Sodium hydride → 1-[4'-(3-Methyl-4-phenethylsulfanylmethyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester

HRID 1528776Notes

Reaction equation

HRID 1528776 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]4[O:27][N:26]=[C:25]([CH3:28])[C:24]=4[CH2:29]Br)=[CH:19][CH:18]=3)=[CH:13][CH:12]=2)[CH2:10][CH2:9]1)=[O:7])[CH3:4].[C:31]1([CH2:37][CH2:38][SH:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]4[O:27][N:26]=[C:25]([CH3:28])[C:24]=4[CH2:29][S:39][CH2:38][CH2:37][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:19][CH:18]=3)=[CH:13][CH:12]=2)[CH2:10][CH2:9]1)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 781262-PhenylethanethiolHCID 665771991-[4'-(4-Bromomethyl-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 665772021-[4'-(3-Methyl-4-phenethylsulfanylmethyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in mineral oil, 0.070 g, 1.70 mmol) was added to a solution of 1-[4′-(4-bromomethyl-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester (0.500 g, 1.13 mmol) and 2-phenylethanethiol (0.15 mL, 1.13 mmol) in DMF. The reaction was stirred at room temperature for 2 hours, and then partitioned between EtOAc and H2O and acidified with 1 N aqueous HCl. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated. Analytical LCMS indicated that a mixture of the title compound and the hydrolyzed acid were present, so the crude material was used directly in the hydrolysis step.

Workup

  1. custompartitioned between EtOAc and H2O
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialthe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionAnalytical LCMS indicated that a mixture of the title compound
  7. customwas used directly in the hydrolysis step

Sources & evidence

ORD record
ord-7b71e9a5590b4a929e83675e0e32fcbd
Source dataset
uspto-grants-2015_07
Patent number
US09090573B2

Reaction notes

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