Triethylamine → (3S,4R)-N-Boc-3-azido-4-acetoxypyrrolidine

Temperature

0 °C

(3S,4S)-3-(4-Phenoxybenzenesulfonamido)-4-mercaptopyrrolidine Hydrochloride. A solution of (3S,4S)—N-Boc-3-azido-4-hydroxypyrrolidine (850 mg, 3.72 mmol) and triethylamine (622 μL, 4.46 mmol) in CH2Cl2 (10 mL) was cooled with stirring to 0° C., and methanesulfonyl chloride (331 μl, 4.28 mmol) was added dropwise. The solution was stirred at room temperature until no starting material was detected by TLC (25% ethyl acetate in hexane). The reaction mixture was washed with 10% aq. citric acid, water, dried over Na2SO4 and evaporated. The residual crude methanesulfonate was dissolved in anhydrous DMF (20 mL), potassium acetate (1.10 g, 11.2 mmol) was added, and the mixture was stirred at 105° C. under nitrogen for 6 hr. The reaction mixture was poured into ice water and was extracted with ethyl acetate (20 ml×3). The organic layer was washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (25% ethyl acetate in hexane) to give (3S,4R)—N-Boc-3-azido-4-acetoxypyrrolidine (860 mg, 86%): 1H NMR (300 MHz, CDCl3) δ 5.31 (br m, 1H), 4.07 (m, 1H), 3.60-3.71 (m, 2H), 3.36-3.50 (m, 2H), 2.16 (s, 3H), 1.46 (s, 9H); [α]20D=−34.5° (c=1.00, CHCl3).

1. stirringThe solution was stirred at room temperature until no starting material
2. washThe reaction mixture was washed with 10% aq. citric acid, water
3. dry with materialdried over Na2SO4
4. customevaporated
5. dissolutionThe residual crude methanesulfonate was dissolved in anhydrous DMF (20 mL)
6. stirringthe mixture was stirred at 105° C. under nitrogen for 6 hr
7. extractionwas extracted with ethyl acetate (20 ml×3)
8. washThe organic layer was washed with brine
9. dry with materialdried over Na2SO4
10. customevaporated
11. customThe residue was purified by flash chromatography (25% ethyl acetate in hexane)

ORD record

ord-7381811f44f34ec6b80d95db319271a4

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404866B2