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3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid

Product Name
3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid
CAS No.
162401-62-9
Chemical Name
3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid
Synonyms
RofluM;Roflumilast Impurity J;Roflumilast Acid Impurity;Roflumilast intermediate B;RofluMilast InterMediate II;Acid Impurity of Roflumilast;Roflumilast Related Compound D;Roflumilast USP Related Compound D;Roflumilast Carboxylic Acid Impurity;CYCLOPROPYL DIFLUOROMETHOXYBENOZOIC ACID
CBNumber
CB02487690
Molecular Formula
C12H12F2O4
Formula Weight
258.22
MOL File
162401-62-9.mol
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3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid Property

Melting point:
118-120℃
Boiling point:
356.4±37.0 °C(Predicted)
Density 
1.355±0.06 g/cm3(Predicted)
storage temp. 
Sealed in dry,Room Temperature
solubility 
DMSO (Slightly), Methanol (Slightly)
form 
Solid
pka
3.87±0.10(Predicted)
color 
White to Off-White
InChI
InChI=1S/C12H12F2O4/c13-12(14)18-9-4-3-8(11(15)16)5-10(9)17-6-7-1-2-7/h3-5,7,12H,1-2,6H2,(H,15,16)
InChIKey
IGFDIFLMMLWKKY-UHFFFAOYSA-N
SMILES
C(O)(=O)C1=CC=C(OC(F)F)C(OCC2CC2)=C1
CAS DataBase Reference
162401-62-9
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Safety

Hazard Codes 
T
Risk Statements 
25
Safety Statements 
45
RIDADR 
2811
HazardClass 
6.1
PackingGroup 
HS Code 
2918999090
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Danger
Hazard statements

H301Toxic if swalloed

Precautionary statements

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
MNO000161
Product name
3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid
Packaging
1g
Price
$104
Updated
2024/03/01
Alfa Aesar
Product number
H64098
Product name
3-Cyclopropylmethoxy-4-difluoromethoxybenzoic acid, 98%
Packaging
1g
Price
$62.9
Updated
2024/03/01
Alfa Aesar
Product number
H64098
Product name
3-Cyclopropylmethoxy-4-difluoromethoxybenzoic acid, 98%
Packaging
5g
Price
$241
Updated
2024/03/01
Alfa Aesar
Product number
H64098
Product name
3-Cyclopropylmethoxy-4-difluoromethoxybenzoic acid, 98%
Packaging
250mg
Price
$20.9
Updated
2023/06/20
TRC
Product number
C988720
Product name
3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid
Packaging
1g
Price
$70
Updated
2021/12/16
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3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid Chemical Properties,Usage,Production

Description

3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid (DGM) is a pharmaceutical intermediate ingredient used in the preparation of Roflumilast, a selective phosphodiesterase-4 (PDE4) inhibitor approved for the treatment of chronic bronchitis and to reduce the risk of exacerbations in patients with severe chronic obstructive pulmonary disease (COPD).

Uses

An impurity and intermediate in the preparation of selective phosphodiesterase 4 (PDE4) inhibitor, Roflumilast (R639700).

Biological Activity

It was shown that 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid (DGM) attenuated transforming growth factor-β1 (TGF-β1)-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in rats. DGM treatment suppressed the expression of proteins such as α-SMA, waveform protein and collagen I and other proteins and increased the expression of E-cadherin. Correspondingly, the phosphorylation level of Smad2/3 was significantly reduced after DGM treatment[1].

Synthesis

3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid is synthesised using 3-cyclopropylmethoxy-4-difluoromethoxybenzaldehyde as raw material by chemical reaction. The specific synthesis steps are as follows:
3-cyclopropylmethoxy-4-difluoromethoxybenzaldehyde (12 g, 50 mmol) and sulfamic acid (7.3 g, 75 mmol) were dissolved in glacial acetic acid (50 ml) and the solution added with a solution of sodium chlorite (8.2 g, 75 mmol) in water (15 ml). The reaction mixture was stirred at room temperature for 1 hr then water (300 ml) was added so obtaining the precipitation of a solid that was filtered and dried at 40° C. under vacuum (12 g, 48 mmol, 97percent yield).

References

[1] TIANXIAO SUN. Inhibitory Effects of 3-Cyclopropylmethoxy-4-(difluoromethoxy) Benzoic Acid on TGF-β1-Induced Epithelial-Mesenchymal Transformation of In Vitro and Bleomycin-Induced Pulmonary Fibrosis In Vivo.[J]. International Journal of Molecular Sciences, 2023. DOI:10.3390/ijms24076172.

3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid Preparation Products And Raw materials

Raw materials

Preparation Products

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3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid Suppliers

TOKYO CHEMICAL INDUSTRY CO., LTD.
Tel
03-36680489
Fax
03-3668-0520
Email
Sales-JP@TCIchemicals.com
Country
Japan
ProdList
28387
Advantage
80
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View Lastest Price from 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid manufacturers

Wuhan Quanjinci New Material Co.,Ltd.
Product
3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid 162401-62-9
Price
US $100.00/kg
Min. Order
1kg
Purity
99%
Supply Ability
5000000 tons
Release date
2023-11-07
Honest Joy Holdings Limited
Product
3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid 162401-62-9
Price
US $0.00/KG
Min. Order
1KG
Purity
99.1%
Supply Ability
100 tons
Release date
2022-02-08
Zhuozhou Wenxi import and Export Co., Ltd
Product
3-Cyclopropylmethoxy-4-difluoromethoxy-benzoic acid 162401-62-9
Price
US $15.00-10.00/KG
Min. Order
1KG
Purity
99%+ HPLC
Supply Ability
Monthly supply of 1 ton
Release date
2021-07-10

162401-62-9, 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic AcidRelated Search:


  • 3-Cyclopropylmethoxy-4-difluoromethoxy-benzoic acid
  • 3-CyclopropyMethoxy-4-difluoroMethoxy benzoic acid
  • Benzoic acid, 3-(cyclopropylMethoxy)-4-(difluoroMethoxy)-
  • CYCLOPROPYL DIFLUOROMETHOXYBENOZOIC ACID
  • 3-CyclopropylMethoxy-4-isopropoxy-benzoic acid
  • RofluMilast InterMediate II
  • Roflumilast intermediate (3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid)
  • Roflumilast Acid Impurity
  • 3-Cyclopropylmethoxy-4-difluoromethoxybenzoic acid, >=98%
  • Roflumilast intermediate B
  • Roflumilast Impurity J
  • RofluM
  • Roflumilast Carboxylic Acid Impurity
  • Roflumilast Related Compound D
  • Roflumilast USP Related Compound D
  • Acid Impurity of Roflumilast
  • 162401-62-9
  • C12H12O4F2
  • Roflumilast interemdiate
  • Intermediates