N-Boc-trans-4-tosyloxy-L-proline methyl ester Chemical Properties

Melting point:

77.0 to 81.0 °C

Boiling point:

508.1±50.0 °C(Predicted)

Density 

1.30±0.1 g/cm3(Predicted)

storage temp. 

Inert atmosphere,2-8°C

solubility 

Chloroform

form 

Solid

pka

-5.65±0.60(Predicted)

color 

White

optical activity

Consistent with structure

λmax

274nm(CHCl3)(lit.)

CAS DataBase Reference

88043-21-4

Safety Information

Hazard Codes 

Xi

Risk Statements 

36

Safety Statements 

26

HS Code 

2933.99.8290

N-Boc-trans-4-tosyloxy-L-proline methyl ester Usage And Synthesis

Chemical Properties

N-Boc-trans-4-tosyloxy-L-proline methyl ester is Colourless crystals

Uses

N-Boc-trans-4-tosyloxy-L-proline methyl ester is used in the preparation of bicycloazahydantoins, as androgen receptor antagonists

Synthesis

General procedure for the synthesis of BOC-trans-4-tosyl-L-proline methyl ester from N-Boc-trans-4-hydroxy-L-proline methyl ester and p-toluenesulfonyl chloride: 1-tert-butyl-2-methyl-(2S,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate (30.00 g, 122.3 mmol) and triethylamine (51.1 mL. 367 mmol) were dissolved in CH2Cl2 (500 mL), followed by the addition of p-toluenesulfonyl chloride (28.0 g, 147 mmol) and 4-dimethylaminopyridine (1.00 g, 8.18 mmol). The reaction mixture was stirred at room temperature overnight.TLC (hexane solution of 50% ethyl acetate) showed that the reaction was incomplete, so 0.5 equivalents (14 g) of p-toluenesulfonyl chloride was added additionally and stirring was continued overnight.After TLC confirmed that the feedstock was completely consumed, the reaction mixture was diluted with 300 mL of CH2Cl2, and the reaction mixture was sequentially diluted with 1.0 N HCl (2 × 100 mL), 1.0 N NaOH ( 2 × 100 mL) and brine (1 × 100 mL) was washed and the organic layer was dried with Na2SO4. The solvent was concentrated under reduced pressure to give a dark colored oil containing crystalline solids. Purification by silica gel column chromatography (450 g silica gel, 25% ethyl acetate in hexane solution) gave 47.4 g (97%) of light brown oily product.1H NMR (400 MHz, CDCl3) δ ppm 1.32-1.48 (m, 9H), 2.07-2.23 (m, 1H), 2.34-2.62 (m, 4H), 3.52- 3.66 (m, 2H), 3.72 (s, 3H), 4.28-4.46 (m, 1H), 4.96-5.12 (m, 1H), 7.33-7.41 (m, 2H), 7.79 (d, J=8.29Hz, 2H); MS ES+ m/z 300.3 (M-99) and 344.3 (M-55).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 24, p. 6107 - 6111
[2] Patent: WO2009/137130, 2009, A2. Location in patent: Page/Page column 182
[3] Patent: WO2018/26792, 2018, A1. Location in patent: Page/Page column 68
[4] Patent: US2008/306086, 2008, A1. Location in patent: Page/Page column 5-6; 15-16
[5] Bulletin of the Korean Chemical Society, 2016, vol. 37, # 8, p. 1259 - 1264

N-Boc-trans-4-tosyloxy-L-proline methyl ester(88043-21-4)Related Product Information

• Methyl acrylate
• cis-4-Hydroxy-L-proline
• D-Proline
• Methylparaben
• Methyl p-toluenesulfonate
• L-PROLINE-(4-3H(N))
• Methanol
• Methyl methoxyacetate
• Acetonitrile
• Basic Violet 1
• Kresoxim-methyl
• N-Boc-trans-4-amino-L-proline methyl ester hydrochloride
• N-Boc-trans-4-Hydroxy-L-proline methyl ester
• N-Boc-trans-4-amino-L-proline methyl ester
• Methyl
• Boc-Hyp-OH
• 1-(tert-Butoxycarbonyl)-3-pyrrolidinol
• (R)-2-Methylpyrrolidine tosylate