Dichloromethane → (3R,4R)-1-Boc-4-fluoro-3-piperidinol

HRID 1923662Notes

Reaction equation

HRID 1923662 reaction equation
[CH:1]12[O:7][CH:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:2]2.[FH:15].F.F.C(N(CC)CC)C.C(=O)(O)[O-].[Na+].C(Cl)Cl>ClCCCl>[F:15][C@@H:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:2][C@H:1]1[OH:7]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 516892Sodium BicarbonateHCID 21991116tert-Butyl 7-Oxa-3-azabicyclo(4.1.0)heptane-3-carboxylate

Product 1

HCID 67086934(3R,4R)-1-Boc-4-fluoro-3-piperidinolYield 58.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (5.46 g, 27.4 mmol) and triethylamine trihydrofluoride (4.42 g, 27.4 mmol) in DCE (4 mL) was stirred at 80° C. (bath) for 18 hours. After cooling to room temperature, saturated sodium bicarbonate (20 mL) and DCM (30 mL) were added. The organic phase was separated, washed with brine, dried (sodium sulfate) and concentrated in vacuo. The residue obtained was purified by flash chromatography on silica gel (hexane:ethyl acetate 1:1) to give trans-tert-butyl 4-fluoro-3-hydroxypiperidine-1-carboxylate (3.5 g, 58%) as a solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe organic phase was separated
  3. washwashed with brine
  4. dry with materialdried (sodium sulfate)
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. customwas purified by flash chromatography on silica gel (hexane:ethyl acetate 1:1)

Sources & evidence

ORD record
ord-f5a089cc60da426c908d9f6bf7f0b5cc
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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