N,N-Diethylethanamine trihydrofluoride → (3R,4R)-tert-Butyl 3-fluoro-4-hydroxypyrrolidine-1-carboxylate

HRID 252090Notes

Reaction equation

HRID 252090 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH:10]([O:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[FH:14].F.F.C(N(CC)CC)C>>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([OH:11])[C@H:10]([F:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 175505N,N-Diethylethanamine trihydrofluorideHCID 10103880tert-Butyl 6-Oxa-3-azabicyclo(3.1.0)hexane-3-carboxylate

Product 1

HCID 57416936(3R,4R)-tert-Butyl 3-fluoro-4-hydroxypyrrolidine-1-carboxylate

Procedure

Stir a mixture of 6-oxa-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (100 mg, 0.54 mmol) and triethylamine trihydrofluoride (88 μL, 0.54 mmol) at 100° C. for 30 min in a microwave (CEM Discover, 300W). Add saturated aqueous sodium hydrogen carbonate and extract with chloroform. Combine the organic layers and wash with saturated aqueous sodium chloride, dry (magnesium sulfate) and concentrate to give trans-3-fluoro-4-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester which may be used without further purification. 1H NMR (300 MHz, CDCl3) δ 4.85 (1H, d, J=50.86 Hz), 4.29 (1H, dd, J=8.01, 2.92 Hz), 3.38-3.65 (4H, m), 1.39 (9H, s).

Workup

  1. extractionAdd saturated aqueous sodium hydrogen carbonate and extract with chloroform
  2. washwash with saturated aqueous sodium chloride
  3. dry with materialdry (magnesium sulfate)
  4. concentrationconcentrate

Sources & evidence

ORD record
ord-42af8363e1f2441a8f1a6f96c9953b1f
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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