Hydrochloric Acid → (R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 2116683Notes

Reaction equation

HRID 2116683 reaction equation
[OH-].[Li+].[O:3]=[C:4]1[NH:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[CH2:7][CH2:6][N:5]1[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C@@H:24]([C:38]([O:40]CC)=[O:39])[CH2:25][C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:29]([NH2:36])=[C:28]([Cl:37])[CH:27]=2)=[O:22])[CH2:17][CH2:16]1.C1COCC1.Cl>O>[O:3]=[C:4]1[NH:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[CH2:7][CH2:6][N:5]1[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C@@H:24]([C:38]([OH:40])=[O:39])[CH2:25][C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[C:29]([NH2:36])=[C:28]([Cl:37])[CH:27]=2)=[O:22])[CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028Tetrahydrofuran2×HCID 69195689(R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-ethoxycarbonyl-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 58202073(R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of 804 mg (33.5 mmol) lithium hydroxide dissolved in 80 ml of water was added dropwise to a mixture of 13.0 g (22.3 mmol) (R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-ethoxycarbonyl-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-benzo[d]-[1,3]diazepin-3-yl)-piperidine-1-carboxylate and 120 ml THF. The mixture was stirred for 3 hours at ambient temperature, freed from THF under reduced pressure, combined with 150 ml of water, and acidified by the addition of aqueous 4-molar hydrochloric acid solution. Then the aqueous phase was extracted with 300 ml of ethyl acetate, the organic phase was dried and evaporated down under reduced pressure. The residue was recrystallised from 50 ml isopropanol.

Workup

  1. extractionThen the aqueous phase was extracted with 300 ml of ethyl acetate
  2. customthe organic phase was dried
  3. customevaporated down under reduced pressure
  4. customThe residue was recrystallised from 50 ml isopropanol

Sources & evidence

ORD record
ord-5679f85149ef4a30969fb1bc5c56ed9d
Source dataset
uspto-grants-2008_10
Patent number
US07439237B2

Reaction notes

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