Sodium hydride → HCID 66578721, compound

HRID 1528754Notes

Reaction equation

HRID 1528754 reaction equation
C([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][CH2:28][OH:29])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])C.Br[CH2:31][CH:32]1[CH2:34][CH2:33]1.[H-].[Na+]>CN(C=O)C>[CH:32]1([CH2:31][O:29][CH2:28][CH2:27][C:22]2[C:23]([CH3:26])=[N:24][O:25][C:21]=2[C:18]2[CH:19]=[CH:20][C:15]([C:12]3[CH:13]=[CH:14][C:9]([C:6]4([C:4]([OH:3])=[O:5])[CH2:7][CH2:8]4)=[CH:10][CH:11]=3)=[CH:16][CH:17]=2)[CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 665772661-{4'-[4-(2-Hydroxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 66578721HCID 66578721, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-{4′-[4-(2-hydroxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester (0.144 g, 0.37 mmol) and (bromomethyl)cyclopropane (0.04 mL, 0.44 mmol) in DMF (1.4 mL) as added sodium hydride (60% in mineral oil, 0.022 g, 0.55 mmol) and the reaction was stirred at room temperature. Analytical LCMS indicated that there was a mixture of products, including the hydrolyzed acid, so the mixture was submitted to aqueous workup procedure and purified by silica gel chromatography (0-100% EtOAc in hexanes). Fractions containing the desired product were purified by preparative HPLC to give the title compound.

Workup

  1. additiona mixture of products
  2. custompurified by silica gel chromatography (0-100% EtOAc in hexanes)
  3. additionFractions containing the desired product
  4. customwere purified by preparative HPLC

Sources & evidence

ORD record
ord-6471dea7dea0483c9aba51c87459cc78
Source dataset
uspto-grants-2015_07
Patent number
US09090573B2

Reaction notes

Loading…