Carbon Tetrachloride → phosphoric acid dibenzyl ester (3S,4S)-4-[2-(4-benzyl-3-hydroxy-piperidin-1-yl)-ethanesulfonyl]-phenyl ester

HRID 2187099Notes

Reaction equation

HRID 2187099 reaction equation
[CH2:1]([C@H:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH2:10][C@H:9]1[OH:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(Cl)(Cl)Cl.C(N(CC)C(C)C)(C)C.[CH2:41]([O:48][P:49]([O-:58])[O:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C([O-])(O)=O.[Na+]>C(#N)C.CN(C1C=CN=CC=1)C>[CH2:1]([C@H:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][P:49](=[O:58])([O:50][CH2:51][C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[O:48][CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH2:10][C@H:9]1[OH:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 5943Carbon TetrachlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9885963(3S,4S)-4-[2-(4-benzyl-3-hydroxy-piperidin-1-yl)-ethanesulfonyl]-phenolHCID 21904359Dibenzylphosphite

Product 1

HCID 86584795phosphoric acid dibenzyl ester (3S,4S)-4-[2-(4-benzyl-3-hydroxy-piperidin-1-yl)-ethanesulfonyl]-phenyl esterYield 83%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 500 mg (133 mmol) (3S,4S)-4-[2-(4-benzyl-3-hydroxy-piperidin-1-yl)-ethanesulfonyl]-phenol in 20 ml acetonitrile were added 0.64 ml (6.7 mmol) CCl4, 16.3 mg (0.13 mmol) DMAP and 0.48 ml (2.9 mmol) N,N-diisopropylethylamine. The reaction mixture was stirred for 15 min at room temperature and 0.43 ml (1.9 mnmol) dibenzylphosphite were added dropwise. After 20 min. 20 ml sat. NaHCO3 solution was added and the aqueous phase was extracted with ethylacetate (3×30 ml) and the combined organic layers were washed with water, dried over MgSO4, filtrated and the solvent was removed under reduced pressure. Purification of the crude product by chromatography over silica gel (ethylacetate/hexane 2/1) yielded 700 mg (11 mmol, 83%) phosphoric acid dibenzyl ester (3S,4S)-4-[2-(4-benzyl-3-hydroxy-piperidin-1-yl)-ethanesulfonyl]-phenyl ester as a colorless solid.

Workup

  1. waitAfter 20 min
  2. extractionthe aqueous phase was extracted with ethylacetate (3×30 ml)
  3. washthe combined organic layers were washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltrated
  6. customthe solvent was removed under reduced pressure
  7. customPurification of the crude product by chromatography over silica gel (ethylacetate/hexane 2/1)

Sources & evidence

ORD record
ord-71e6e8348b5545c2b3ae3494bb159a81
Source dataset
uspto-grants-2002_06
Patent number
US06407235B1

Reaction notes

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