Hydrochloric Acid → 3-tert-Butoxycarbonyl-6-(4-carboxy-3-fluorobenzylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041402Notes

Reaction equation

HRID 2041402 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([O:30]C)=[O:29])=[C:24]([F:32])[CH:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].Cl>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([OH:30])=[O:29])=[C:24]([F:32])[CH:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 576565573-tert-butoxycarbonyl-7-chloro-6-(3-fluoro-4-methoxycarbonylbenzylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 576559683-tert-Butoxycarbonyl-6-(4-carboxy-3-fluorobenzylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 101%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Heat a stirred solution of 3-tert-butoxycarbonyl-7-chloro-6-(3-fluoro-4-methoxycarbonylbenzylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (3.56 g, 7.44 mmol) in THF (50 mL) and water (40 mL) overnight at 65° C. in the presence of potassium hydroxide (8.30 g, 148.77 mmol). Cool the mixture to 0° C., add slowly a 1N solution of hydrochloric acid until pH 5. Extract three times with EtOAc, dry over anhydrous Na2SO4 and concentrate in vacuo to provide the desired intermediate as a white solid (3.5 g, 99%).

Workup

  1. extractionExtract three times with EtOAc
  2. dry with materialdry over anhydrous Na2SO4
  3. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-abfbece2536e40a29a7ebf6f90e48b1b
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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