Hydrochloric Acid → (1R,2S,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzylsulfanyl)-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 2-ethyl ester

HRID 130514Notes

Reaction equation

HRID 130514 reaction equation
O.[OH-].[Li+].[CH2:4]([O:6][C:7]([C@:9]1([NH2:31])[C@H:14]([S:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH2:13][C@@H:12]2[C@H:10]1[C@@:11]2([F:30])[C:25]([O:27]CC)=[O:26])=[O:8])[CH3:5].Cl>O1CCCC1.O>[CH3:5][CH2:4][O:6][C:7]([C@:9]1([NH2:31])[C@H:14]([S:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH2:13][C@@H:12]2[C@H:10]1[C@@:11]2([F:30])[C:25]([OH:27])=[O:26])=[O:8]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 11442306(1R,2S,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzylsulfanyl)-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester

Product 1

HCID 69306797(1R,2S,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzylsulfanyl)-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 2-ethyl esterYield 51.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

17 mg of lithium hydroxide monohydrate was added to 150 mg of (1R,2S,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzylsulfanyl)-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester dissolved in a mixture of 3.5 mL tetrahydrofuran and 1.7 mL of water, and the mixture was stirred for 30 minutes at ice-cooling. The mixture was acidified to pH 2 with 1N hydrochloric acid, diluted with 30 mL of water, and then stirred for 30 minutes at ice-cooling. This diluted solution was purified by ion exchange resin (AG 50W-X8 Resin (H form), eluent: water, a 30% aqueous solution of tetrahydrofuran and a 10% aqueous solution of pyridine), thereby yielding 73 mg of (1R,2S,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzylsulfanyl)-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 2-ethyl ester.

Workup

  1. temperaturecooling
  2. stirringstirred for 30 minutes at ice-
  3. temperaturecooling
  4. customThis diluted solution was purified by ion exchange resin (AG 50W-X8 Resin (H form), eluent

Sources & evidence

ORD record
ord-bc4c17f9e4e6421e81507e7e0f5cc510
Source dataset
uspto-grants-2008_06
Patent number
US07381746B2

Reaction notes

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