Water → (S)-2-(4-bromo-1-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid

HRID 2378699Notes

Reaction equation

HRID 2378699 reaction equation
[Br:1][C:2]1[C:10]2[NH:9][N:8]=[C:7]([Cl:11])[C:6]=2[C:5]2[CH2:12][N:13]([CH2:23][C:24]([F:27])([F:26])[F:25])[C:14](=[O:22])[C@H:15]([CH2:17][C:18]([O:20]C)=[O:19])[CH2:16][C:4]=2[CH:3]=1.O.O.[OH-].[Li+]>O1CCCC1.CO>[Br:1][C:2]1[C:10]2[NH:9][N:8]=[C:7]([Cl:11])[C:6]=2[C:5]2[CH2:12][N:13]([CH2:23][C:24]([F:25])([F:26])[F:27])[C:14](=[O:22])[C@H:15]([CH2:17][C:18]([OH:20])=[O:19])[CH2:16][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrate2×HCID 178500647HCID 178500647, compound

Product 1

HCID 178525537(S)-2-(4-bromo-1-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

(S)-Methyl 2-(4-bromo-1-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetate (210 mg, 0.448 mmol) was dissolved in a mixture of tetrahydrofuran (3.0 ml) and methanol (3.0 ml). Water (3.00 ml) was added to the mixture followed by lithium hydroxide hydrate (30 mg, 0.715 mmol). Reaction was warmed to 50° C. and held with stirring for 5 hours. Mixture was cooled to room temperature and allowed to stand for 64 hours. More lithium hydroxide hydrate (24.9 mg, 0.593 mmol) was added to the mixture. Reaction was warned to 50° C. and held for 3 hours. Mixture was cooled to room temperature. Organic solvents were removed from the mixture by roto-vap. Residue was diluted with water. Mixture was neutralized with 1.4 mL 1N hydrochloric acid. Material was extracted twice with ethyl acetate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as off-white solid in quantitative yield. LCMS (M−H)−=453.9.

Workup

  1. customReaction
  2. temperatureMixture was cooled to room temperature
  3. waitto stand for 64 hours
  4. customReaction
  5. customwas warned to 50° C.
  6. waitheld for 3 hours
  7. temperatureMixture was cooled to room temperature
  8. customOrganic solvents were removed from the mixture by roto-vap
  9. additionResidue was diluted with water
  10. extractionMaterial was extracted twice with ethyl acetate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-e67e502a32c5481faba55b748bc19c3f
Source dataset
uspto-grants-2008_12
Patent number
US07470679B2

Reaction notes

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