(S)-1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl)ethanaMine Chemical Properties

Melting point:

106-108oC

Boiling point:

469.6±45.0 °C(Predicted)

Density 

1.195±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

6.84±0.10(Predicted)

form 

Solid

color 

White to Off-White

InChI

InChI=1/C12H19NO4S/c1-4-17-12-7-9(5-6-11(12)16-2)10(13)8-18(3,14)15/h5-7,10H,4,8,13H2,1-3H3/t10-/s3

InChIKey

BXUJVINGXQGNFD-JQHDBZEONA-N

SMILES

[C@@H](C1C=CC(OC)=C(OCC)C=1)(N)CS(=O)(=O)C |&1:0,r|

Safety Information

HS Code 

2930909899

(S)-1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl)ethanaMine Usage And Synthesis

Chemical Properties

APREMILAST intermediate is slightly soluble in dichloromethane and soluble in methanol. It is mainly used to synthesize APREMILAST. In addition, it can also regulate intracellular pro-inflammatory and anti-inflammatory factor effects through specificity for cyclic adenosine monophosphate (c AMP), which increases intracellular cAMP levels.

Uses

(1S)-1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine is an Apremilast (A729700) intermediate. Apremilast, an oral phosphodiesterase 4 inhibitor is used in the treatment of psoriatic arthritis.

Synthesis

The general procedure for the synthesis of (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine from the compound (CAS: 1450657-31-4) was as follows: bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate (36 mg, 0.074 mmol) and (S)-1-[(R)-2- ( diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (40 mg, 0.074 mmol) were dissolved in 25 mL of 2,2,2-trifluoroethanol. Subsequently, 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine (2.0 g, 7.4 mmol) was added to this solution. The reaction mixture was heated to 50 °C and hydrogenated under hydrogen pressure of 90 psig. After 18 h, the mixture was cooled to room temperature and removed from the hydrogenation unit. The solvent was removed by rotary evaporation and the residue was purified by chromatography on a C18 reversed-phase column using a water-acetonitrile gradient elution. The fraction containing the target product was collected and concentrated to about 150 mL. saturated brine (20 mL) was added to the concentrate and subsequently extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered and concentrated to give a white crystalline solid product (1.4 g, 70% yield). The product was analyzed by non-chiral HPLC (Hypersil BDSC8, 5.0 μm, 250 × 4.6 mm, 1.5 mL/min, 278 nm, 90/10 to 80/20 0.1% TFA aqueous solution/methanol gradient elution for 10 min, followed by a gradient up to 10/90 0.1% TFA aqueous solution/methanol for the next 15 min). Retention time was 9.11 min (99.6% purity); chiral HPLC (Chiralpak AD-H 5.0 μm Daicel, 250 × 4.6 mm, 1.0 mL/min, 280 nm, 70:30:0.1 heptane-isopropanol-diethylamine) analyzed with retention times of 7.32 min (97.5%) and 8.26 min ( 2.47%).1H NMR (DMSO-d6) δ 1.32 (t, J = 7.0 Hz, 3H), 2.08 (s, 2H), 2.96 (s, 3H), 3.23 (dd, J = 3.6, 14.4 Hz, 1H), 3.41 (dd, J = 9.4, 14.4 Hz, 1H), 3.73 (s, 3H), 4.02 (q , J = 7.0 Hz, 2H), 4.26 (dd, J = 3.7, 9.3 Hz, 1H), 6.89 (s, 2H), 7.02 (s, 1H); 13C NMR (DMSO-d6) δ 14.77, 41.98, 50.89, 55.54, 62.03, 63.68, 111.48, 111.77, 118.36, 137.30, 147.93, 148.09.

References

[1] Patent: US2014/81032, 2014, A1. Location in patent: Paragraph 0318; 0319
[2] Patent: US2013/217919, 2013, A1. Location in patent: Paragraph 0280
[3] Patent: WO2016/199031, 2016, A1

(S)-1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl)ethanaMine(608141-42-0)Related Product Information

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