Water → HCID 89649041, compound
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].Br[C:16]([F:25])([F:24])[C:17]([N:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1)=[O:18].O>CC(N(C)C)=O.C1(C)C=CC=CC=1>[F:24][C:16]([F:25])([O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)[C:17]([N:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1)=[O:18]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 120 °C
Procedure
To a mixture of 3-fluoro-phenol (4.5 g, 40.0 mmol), and K2CO3 (6.1 g, 44.0 mmol) in 40 g of DMAC at 100° C. was added 2-bromo-2,2-difluoro-1-pyrrolidine-1-yl-ethanone (9.1 g, 40.0 mmol). The mixture was kept at that temperature for 1 h and then heated to 120° C. for 2 h. The reaction mixture was then cooled to room temperature and poured on 120 mL of H2O and 30 mL of toluene. The aqueous phase was extracted with 25 g of toluene. The combined organic layers were extracted with 10% NaOH (10 g) and H2O (2×15 g) and dried over Na2SO4. The product (8.3 g, >90% purity by NMR) was obtained after removal of all volatiles under reduced pressure as a slightly yellow liquid. The material could be used in subsequent steps without further purification.
Workup
- temperatureThe reaction mixture was then cooled to room temperature
- extractionThe aqueous phase was extracted with 25 g of toluene
- extractionThe combined organic layers were extracted with 10% NaOH (10 g) and H2O (2×15 g)
- dry with materialdried over Na2SO4
- customThe product (8.3 g, >90% purity by NMR) was obtained
- customafter removal of all volatiles under reduced pressure as a slightly yellow liquid
- customThe material could be used in subsequent steps without further purification
Sources & evidence
- ORD record
- ord-b98c20f1ddf64f39bef5de1b4b246eca
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09365495B2
Reaction notes
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