Lithium Hydroxide → 3-tert-butoxycarbonyl-6-(5-carboxypyridin-2-ylmethylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911469Notes

Reaction equation

HRID 911469 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])=[CH:24][N:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH:10](Cl)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>CO.Cl>[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])=[CH:24][N: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

5

Reactant 2

HCID 3939Lithium HydroxideHCID 667072413-tert-butoxycarbonyl-7-chloro-6-(5-methoxycarbonyl-pyridin-2-ylmethylthio)-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 576562583-tert-butoxycarbonyl-6-(5-carboxypyridin-2-ylmethylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 98.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent2×

Procedure

Dissolve 3-tert-butoxycarbonyl-7-chloro-6-(5-methoxycarbonyl-pyridin-2-ylmethylthio)-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.86 g, 4.03 mmol) in methanol (25 mL). Add 1M aqueous lithium hydroxide (12 mL) and stir at ambient temperature overnight. Remove methanol in vacuo, and dilute the mixture with cold 0.5M aqueous HCl to pH 4. Add brine and extract three times with EtOAc. Dry over anhydrous Na2SO4, and concentrate in vacuo to give the title compound as an off-white solid (1.78 g, 95%). MS (APCI+) m/z 449 (M+H)+, 349 (M+H−Boc)+.

Workup

  1. extractionAdd brine and extract three times with EtOAc
  2. dry with materialDry over anhydrous Na2SO4
  3. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-69aaef07316e41be84d9e8fe12b940af
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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