Sodium Bicarbonate → Benzyl piperidine-1-carboxylate

HRID 2303394Notes

Reaction equation

HRID 2303394 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@:14](CC2C=CC=CC=2)(O)[C@@H:13](O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 59904582HCID 59904582, compound

Product 1

HCID 228749Benzyl piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 43.0 g (126 mmol) (3R,4R) and (3S,4S)-4-benzyl-3,4-dihydroxy-piperidine-1-carboxylic acid benzyl ester and 23.1 g (189 mmol) DMAP in 600 ml CH2Cl2 were added dropwise under argon 500 ml (340 mmol, 0.70 N) (S)-N-trifluoroacetyl-prolinechloride. The reaction mixture was stirred for 16 hours at r.t. and then sat. NaHCO3 solution was added. The aqueous phase was extracted three times with CH2Cl2 and the combined organic layers were washed with sat. NaHCO3 and 1N HCl, dried over MgSO4 and the solvent was removed under reduced pressure to give the crude product. Purification by chromatography on silica gel (hexane:ethyl acetate 4:1 to 1:1) and crystallization from diethylether yielded 17.9 g (33 mmol, 27%) (3R,4R), 4-benzyl-4-hydroxy-3-(2S)-trifluoroacetyl-cyclopentanecarbonyloxy)-piperidine-1-carboxylic acid benzyl ester.

Workup

  1. extractionThe aqueous phase was extracted three times with CH2Cl2
  2. washthe combined organic layers were washed with sat. NaHCO3 and 1N HCl
  3. dry with materialdried over MgSO4
  4. customthe solvent was removed under reduced pressure
  5. customto give the crude product
  6. customPurification by chromatography
  7. customon silica gel (hexane:ethyl acetate 4:1 to 1:1) and crystallization from diethylether

Sources & evidence

ORD record
ord-07a48b3c0a924880a0fecf404e10bc24
Source dataset
uspto-grants-2002_08
Patent number
US06432985B1

Reaction notes

Loading…