Sodium Bicarbonate → tert-Butyl (3S)-3-fluoropyrrolidine-1-carboxylate

HRID 1445771Notes

Reaction equation

HRID 1445771 reaction equation
COCCN(S(F)(F)[F:11])CCOC.[C:14]([N:21]1[CH2:25][CH2:24][C@@H:23](O)[CH2:22]1)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(=O)([O-])O.[Na+]>ClCCl>[F:11][C@H:23]1[CH2:24][CH2:25][N:21]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:22]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 18453464tert-Butyl (3S)-3-fluoropyrrolidine-1-carboxylateYield 81.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Slowly add [bis(2-methoxyethyl)amino]sulfur trifluoride (2.40 mL, 13.03 mmol) to a solution of N-Boc-(R)-(−)-3-pyrrolidinol (2.00 g, 10.86 mmol) in anhydrous dichloromethane (10 mL), at −78° C. and under nitrogen. Allow the reaction mixture to warm to room temperature and stir overnight. Carefully add an aqueous solution of sodium hydrogen carbonate (saturated, 20 mL) and extract with dichloromethane. Concentrate the combined organic extracts under vacuum then purify using automated flash chromatography (ISCO® System, 120 g Redisep® SiO2 column; 0-40% ethyl acetate in cyclohexane gradient elution over 30 minutes at 85 mL/min) to give the title compound as a pale yellow liquid (1.67 g): MS (m/e): 212 (M+23).

Workup

  1. customat −78° C.
  2. extractionextract with dichloromethane
  3. concentrationConcentrate the combined organic extracts under vacuum
  4. customthen purify
  5. washflash chromatography (ISCO® System, 120 g Redisep® SiO2 column; 0-40% ethyl acetate in cyclohexane gradient elution over 30 minutes at 85 mL/min)

Sources & evidence

ORD record
ord-b91f0bc6101b430d8fa5df236e3fe673
Source dataset
uspto-grants-2010_02
Patent number
US07666871B2

Reaction notes

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