Potassium Carbonate → Methyl 2-(4-bromo-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetate

HRID 1525901Notes

Reaction equation

HRID 1525901 reaction equation
Br[CH:2]([C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][C:8]=1[F:14])[C:3]([O:5][CH3:6])=[O:4].C(=O)([O-])[O-].[K+].[K+].Cl.[CH:22]1([N:25]2[CH2:30][C:29]3([CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[O:28][CH2:27][C:26]2=[O:36])[CH2:24][CH2:23]1>CN(C)C=O.O>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([CH:2]([N:33]2[CH2:34][CH2:35][C:29]3([O:28][CH2:27][C:26](=[O:36])[N:25]([CH:22]4[CH2:23][CH2:24]4)[CH2:30]3)[CH2:31][CH2:32]2)[C:3]([O:5][CH3:6])=[O:4])=[C:8]([F:14])[CH:9]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 53429414Methyl 2-bromo-2-(4-bromo-2-fluorophenyl)acetateHCID 69083351HCID 69083351, compound

Product 1

HCID 71270944Methyl 2-(4-bromo-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetateYield 91.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 2-bromo-2-(4-bromo-2-fluorophenyl)acetate (7.29 mmol) in N,N-dimethylformamide (30 mL) was treated with potassium carbonate (19.90 mmol) and 4-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride (8.31 mmol). The reaction was stirred at room temperature for two days. The reaction solution was diluted with water (200 mL) and was extracted three times with ethyl acetate. The combined organic layers were washed five times with water and three times with brine. The organic solution was dried over sodium sulfate, filtered and concentrated in vacuo. The resulting semi-solid was diluted with dichloromethane (10 mL) and was concentrated to dryness in vacuo. This was repeated twice, at which point the resulting solid was dried under high vacuum overnight, affording the title compound as a white solid (3.05 g, 87% yield). MS(ES)+ m/e 454.8/456.9 [M+H]+ (bromide isotope pattern).

Workup

  1. extractionwas extracted three times with ethyl acetate
  2. washThe combined organic layers were washed five times with water and three times with brine
  3. dry with materialThe organic solution was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionThe resulting semi-solid was diluted with dichloromethane (10 mL)
  7. concentrationwas concentrated to dryness in vacuo
  8. customwas dried under high vacuum overnight

Sources & evidence

ORD record
ord-095f29ec5e804714b77fd2fd13ec755e
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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