Ammonium Chloride → [10-(5-Fluoro-3-pyridyl)-8-hydroxy-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

HRID 1478449Notes

Reaction equation

HRID 1478449 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[O:31][C:12]3([CH2:17][CH2:16][N:15]([C:18](=[O:30])[C:19]4[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH3:29])[CH:20]=4)[CH2:14][CH2:13]3)[CH2:11][C:10](=[O:32])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.[BH4-].[Na+].[Cl-].[NH4+]>CO>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[O:31][C:12]3([CH2:17][CH2:16][N:15]([C:18]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH3:29])[CH:20]=4)=[O:30])[CH2:14][CH2:13]3)[CH2:11][CH:10]([OH:32])[CH:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 8970851210-(5-Fluoro-3-pyridyl)-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3-azaspiro[5.5]undec-9-en-8-one

Product 1

HCID 89704548[10-(5-Fluoro-3-pyridyl)-8-hydroxy-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanoneYield 93.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 10-(5-fluoro-3-pyridyl)-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3-azaspiro[5.5]undec-9-en-8-one (273 mg, 0.62 mmol) in methanol (7.8 mL) was slowly added sodium borohydride (25 mg, 0.65 mmol) The reaction mixture was allowed to stir for 30 minutes. A solution of saturated aqueous ammonium chloride (50 mL) was added. After brief stirring, the mixture was concentrated to half volume and was extracted with dichloromethane (3×75 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified on silica gel utilizing a gradient of 60-100% ethyl acetate in hexanes to yield [10-(5-fluoro-3-pyridyl)-8-hydroxy-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (256 mg) as a colorless oil. ESI-MS m/z calc. 440.2, found 441.3 (M+1)+; Retention time: 1.73 minutes (3 min run).

Workup

  1. concentrationAfter brief stirring, the mixture was concentrated to half volume
  2. extractionwas extracted with dichloromethane (3×75 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified on silica gel utilizing a gradient of 60-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d79f94c583bb4fb4ab4043b018e673a8
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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