1-Chloro-4-(chloromethyl)benzene → [(6R,7S)-9-(4-chloro-benzyl)-6-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl]-carbamic acid tert-butyl ester

HRID 1348599Notes

Reaction equation

HRID 1348599 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[O:10][C@@H:9]1[CH3:20])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Cl)=[CH:27][CH:26]=1>CN(C)C=O>[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]1[C:14](=[O:15])[N:13]([CH2:29][C:28]2[CH:31]=[CH:32][C:25]([Cl:24])=[CH:26][CH:27]=2)[C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[O:10][C@@H:9]1[CH3:20])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 54137235((6R,7S)-6-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-carbamic acid tert-butyl ester

Product 1

HCID 67076947[(6R,7S)-9-(4-chloro-benzyl)-6-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl]-carbamic acid tert-butyl esterYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 0.10 g (342 mmol) ((6R,7S)-6-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-carbamic acid tert-butyl ester in 1 ml dimethylformamide was added at 0° C. over a period of 20 minutes to a suspension of 0.015 g (342 mmol) sodiumhydride (55%) in 2 ml dimethylformamide. After 30 minutes 0.056 g (342 mmol) 4-chlorobenzylchloride was added and stirring was continued for 3 hours at 0° C. Extraction with water/ethylacetate and chromatography on silicagel with ethylacetate/heptane yielded 0.12 g (84%) [(6R,7S)-9-(4-chloro-benzyl)-6-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl]-carbamic acid tert-butyl ester as white solid, MS m/e (%): 417.2 (M+H+, 69), 361.2 (100), 317.1 (91).

Workup

  1. extractionExtraction with water/ethylacetate and chromatography on silicagel with ethylacetate/heptane

Sources & evidence

ORD record
ord-115dc9a3eff349d694180e9cf3b353ba
Source dataset
uspto-grants-2007_05
Patent number
US07211573B2

Reaction notes

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