Triethylamine → 2,2,2-Trifluoro-1-(9-(3-fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone
Reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH2:10][CH2:11][OH:12])[CH:6]=[C:7]([F:9])[CH:8]=1.FC(F)(F)C(O)=O.[F:20][C:21]([F:36])([F:35])[C:22]([N:24]1[CH2:29][C:28]2([CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[O:27][CH2:26][CH2:25]1)=[O:23].C(N(CC)CC)C>C(#N)C>[F:36][C:21]([F:20])([F:35])[C:22]([N:24]1[CH2:29][C:28]2([CH2:34][CH2:33][N:32]([CH2:2][C:3]3[CH:4]=[C:5]([CH2:10][CH2:11][OH:12])[CH:6]=[C:7]([F:9])[CH:8]=3)[CH2:31][CH2:30]2)[O:27][CH2:26][CH2:25]1)=[O:23]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 20 °C
Procedure
A solution of 2-(3-(bromomethyl)-5-fluorophenyl)ethanol (example 41, step b) (3.6 g) and 2,2,2-trifluoro-1-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone trifluoroacetate (example 12, step d) (5.66 g) in acetonitrile (80 mL) was treated with triethylamine (5.38 mL) and the mixture stirred at 20° C. for 20 hours. The solvent was evaporated under reduced pressure and the residue partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulphate, filtered and the solvent removed under reduced pressure. The crude product was purified by flash silica chromatography using 2.5% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 4.9 g.
Workup
- customThe solvent was evaporated under reduced pressure
- customthe residue partitioned between ethyl acetate and brine
- dry with materialThe organic layer was dried over sodium sulphate
- filtrationfiltered
- customthe solvent removed under reduced pressure
- customThe crude product was purified by flash silica chromatography
- customPure fractions were evaporated to dryness
Sources & evidence
- ORD record
- ord-dc5d9a6b5a3c442bada883255e855e41
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08629271B2
Reaction notes
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