Sodium hydride → HCID 21188814, compound

HRID 1384018Notes

Reaction equation

HRID 1384018 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[OH:8][C:9]1[C:17]2[N:16]=[C:15]([CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:14]([CH2:27][CH2:28][CH2:29][CH:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)[C:13]=2[CH:12]=[CH:11][CH:10]=1.[H-].[Na+].[CH:45]1(Br)[CH2:47][CH2:46]1>CN(C)C=O>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH:3]1([O:8][C:9]2[C:17]3[N:16]=[C:15]([CH2:18][O:19][C:20]4[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=4)[N:14]([CH2:27][CH2:28][CH2:29][CH:30]4[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:34][CH2:35]4)[C:13]=3[CH:12]=[CH:11][CH:10]=2)[CH2:2][CH2:47][CH2:45][CH2:46]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 78037BromocyclopropaneHCID 21188826HCID 21188826, compound

Product 1

HCID 21188814HCID 21188814, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-hydroxy-2-[(4-chlorophenoxy)methyl]-1-[3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl]benzimidazole trifluoroacetate (300 mg, 0.6 mmol, 1 eq) in anhydrous N,N-dimethylformamide (3 m) was treated with sodium hydride (60% in mineral oil, 26 mg, 0.66 mmol, 1.1 eq). The resulting mixture was stirred for thirty minutes at room temperature. Cyclopropyl bromide (0.66 mmol, 1 eq) was added to the reaction and the resulting mixture was stirred for two hours at room temperature. The reaction was quenched with the addition of water (5 ml). The aqueous fraction was extracted with ethyl acetate (3×10 ml). The organic fractions were combined, washed with water (2×10 ml), then brine (1×10 ml), and then dried over sodium sulfate. The solvents were removed in vacuo. The residue was further purified by flash column chromatography to yield the title product as a crystalline product in 50% yield.

Workup

  1. stirringthe resulting mixture was stirred for two hours at room temperature
  2. customThe reaction was quenched with the addition of water (5 ml)
  3. extractionThe aqueous fraction was extracted with ethyl acetate (3×10 ml)
  4. washwashed with water (2×10 ml)
  5. dry with materialbrine (1×10 ml), and then dried over sodium sulfate
  6. customThe solvents were removed in vacuo
  7. customThe residue was further purified by flash column chromatography

Sources & evidence

ORD record
ord-51dd9cc8e7f845eaa095f74286bae4ef
Source dataset
uspto-grants-2001_07
Patent number
US06255494B1

Reaction notes

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