Dimethylformamide → (+)-4,5-dihydro-1-[[[(2,2-dimethyl-1-oxopropoxy)methoxy](4-phenylbutyl)phosphinyl]acetyl]-3-phenyl-1H-pyrazole-5-carboxylic acid, phenylmethyl ester

HRID 1757941Notes

Reaction equation

HRID 1757941 reaction equation
[OH:1][P:2]([CH2:14][C:15]([N:17]1[CH:21]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:20][C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:18]1)=[O:16])([CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:3].CN(C)C=O.[C:43]([O:49][CH2:50]Cl)(=[O:48])[C:44]([CH3:47])([CH3:46])[CH3:45].C(N(CC)CC)C>C(OCC)(=O)C>[CH3:45][C:44]([CH3:47])([CH3:46])[C:43](=[O:48])[O:49][CH2:50][O:3][P:2]([CH2:14][C:15]([N:17]1[CH:21]([C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[CH2:20][C:19]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[N:18]1)=[O:16])([CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:1]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 87885Chloromethyl pivalateHCID 86738774(+)-4,5-dihydro-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-3-phenyl-1H-pyrazole-5-carboxylic acid, phenylmethyl ester

Product 1

HCID 86738775(+)-4,5-dihydro-1-[[[(2,2-dimethyl-1-oxopropoxy)methoxy](4-phenylbutyl)phosphinyl]acetyl]-3-phenyl-1H-pyrazole-5-carboxylic acid, phenylmethyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4.0 g. of the benzyl ester product from part (c) dissolved in 40 ml. of dry dimethylformamide under argon is treated at ambient temperature with 1.5 g. of chloromethyl pivalate and 1.8 g. of triethylamine. After stirring overnight, the solution is diluted with ethyl acetate and washed with 10% potassium dihydrogen sulfate, water, and saturated brine. The organic solution is dried (MgSO4) and concentrated in vacuo to give the crude product. Flash chromatography on silica gel and elution with ethyl acetate/dichloromethane (1:1) gives homogeneous (+)-4,5-dihydro-1-[[[(2,2-dimethyl-1-oxopropoxy)methoxy](4-phenylbutyl)phosphinyl]acetyl]-3-phenyl-1H-pyrazole-5-carboxylic acid, phenylmethyl ester as an oil.

Workup

  1. washwashed with 10% potassium dihydrogen sulfate, water, and saturated brine
  2. dry with materialThe organic solution is dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. washFlash chromatography on silica gel and elution with ethyl acetate/dichloromethane (1:1)

Sources & evidence

ORD record
ord-da0631405b4045a2befbd45906ad855f
Source dataset
uspto-grants-1983_02
Patent number
US04371526

Reaction notes

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