Water → 4-fluoro-benzenesulfonic acid 2-[tert-butoxycarbonyl-(3-chloro-4-methoxy-benzyl)-amino]-3H-benzoimidazol-5-yl ester

HRID 1823788Notes

Reaction equation

HRID 1823788 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[NH:13][C:12]2[CH:14]=[CH:15][C:16]([O:18][S:19]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)(=[O:21])=[O:20])=[CH:17][C:11]=2[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[O:40][CH3:41])[CH2:35]Br.O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]([CH2:35][C:34]1[CH:37]=[CH:38][C:39]([O:40][CH3:41])=[C:32]([Cl:31])[CH:33]=1)[C:9]1[NH:10][C:11]2[CH:17]=[C:16]([O:18][S:19]([C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)(=[O:20])=[O:21])[CH:15]=[CH:14][C:12]=2[N:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 114703704-(Bromomethyl)-2-chloro-1-methoxybenzeneHCID 178452971HCID 178452971, compound

Product 1

HCID 865960824-fluoro-benzenesulfonic acid 2-[tert-butoxycarbonyl-(3-chloro-4-methoxy-benzyl)-amino]-3H-benzoimidazol-5-yl esterYield 31.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A stirred solution of 4-fluoro-benzenesulfonic acid 2-tert-butoxycarbonylamino-3H-benzoimidazol-5-yl ester (Example 55 (step 3), 200 mg) in dry dimethylformamide (3 ml) was treated with sodium hydride (12 mg, 60% dispersion in mineral oil). After stirring for 30 minutes the mixture was treated with a solution of 3-chloro-4-methoxy-benzyl bromide (94 mg) in dimethylformamide (1 ml) and stirring was continued for a further 3 hours. The reaction mixture was poured into water (10 ml) and then extracted three times with ethyl acetate (10 ml). The combined extracts were dried over magnesium sulfate and then evaporated. The residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and heptane (1:2, v/v) to give 4-fluoro-benzenesulfonic acid 2-[tert-butoxycarbonyl-(3-chloro-4-methoxy-benzyl)-amino]-3H-benzoimidazol-5-yl ester (70 mg) as a beige solid.

Workup

  1. stirringstirring
  2. waitwas continued for a further 3 hours
  3. extractionextracted three times with ethyl acetate (10 ml)
  4. dry with materialThe combined extracts were dried over magnesium sulfate
  5. customevaporated
  6. additionThe residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and heptane (1:2

Sources & evidence

ORD record
ord-9b280fe86eb9409b98e86e4619ee9f90
Source dataset
uspto-grants-2006_05
Patent number
US07041668B2

Reaction notes

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