Water → HCID 59732071, compound

HRID 132447Notes

Reaction equation

HRID 132447 reaction equation
C([O:9][C@H:10]1[C:24](=[O:25])[N:23]([CH2:26][C:27]([F:30])([F:29])[F:28])[CH2:22][C:13]2[C:14]3[CH:15]=[N:16][NH:17][C:18]=3[C:19]([Cl:21])=[CH:20][C:12]=2[CH2:11]1)(=O)C1C=CC=CC=1.C1COCC1.[OH-].[Li+].O>>[Cl:21][C:19]1[C:18]2[NH:17][N:16]=[CH:15][C:14]=2[C:13]2[CH2:22][N:23]([CH2:26][C:27]([F:28])([F:30])[F:29])[C:24](=[O:25])[C@H:10]([OH:9])[CH2:11][C:12]=2[CH:20]=1

Participants

5

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 59732073(R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl benzoate

Product 1

HCID 59732071HCID 59732071, compoundYield 53%

Procedure

(R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl benzoate (7.00 g, 16.0 mmol) in THF (60.00 ml, 732 mmol) was added lithium hydroxide (0.766 g, 32.0 mmol) followed by water (6.0 ml, 333 mmol). After 3 h, the solvent was removed and the crude product was diluted with dichloromethane and neutralized with 1.0 M HCl. The organic phase was dried and the crude product was purified by flash chromatography using 70% EtOAc in hexane to give (R)-4-chloro-7-hydroxy-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one in 53% yield. 1H NMR (500 MHz, CDCl3): in δ 8.12 (s, 1H), 7.16 (s, 1H), 5.18-5.14 (m, 2H), 4.55 (d, J=17 Hz, 1H), 4.30-4.28 (m, 1H), 4.27-4.24 (m, 1H), 3.86 (m, 1H), 3.46 (dd, J=5 Hz, J=1.5 Hz, 1H), 3.09 (dd, J=5 Hz, J=1.5 Hz, 1H), 1.52 (s, 9H); MS (ESI) 334 (M+H); Rf=1.49.

Workup

  1. customthe solvent was removed
  2. additionthe crude product was diluted with dichloromethane and neutralized with 1.0 M HCl
  3. customThe organic phase was dried
  4. customthe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-0a2c99084183417c8ff1f6fce041bf0e
Source dataset
uspto-grants-2008_06
Patent number
US07384931B2

Reaction notes

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