Triethylamine → 1-(3-Fluoro-4-methoxyphenyl)-4-(hydroxymethyl)pyrrolidin-2-one
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:10]2[C:14](=[O:15])[CH2:13][CH:12]([C:16](O)=[O:17])[CH2:11]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].CCN(CC)CC.ClC(OCC(C)C)=O.[BH4-].[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N:10]2[CH2:11][CH:12]([CH2:16][OH:17])[CH2:13][C:14]2=[O:15])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 1-(3-fluoro-4-methoxyphenyl)-5-oxopyrrolidine-3-carboxylic acid (Step 1, 2 g, 7.9 mmol), Et3N (1.65 mL, 9.48 mmol) in 30 mL of CH2Cl2 at 0° C. was added isobutyl chloroformate (1.23 mL, 9.48 mmol) via a syringe. The reaction was stirred at 0° C. for 1 h. The white precipitate was removed by filtration. The filtrate was cooled to 0° C. and NaBH4 (0.9 g, 23.7 mmol) in water solution (3 mL) was added to the reaction. After 1 h, the mixture was diluted with 100 mL of EtOAc and 30 mL of satd. NaHCO3 solution. The organic phase was separated and washed with 30 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was chromatographed by a silica gel column (5% to 80% EtOAc/hexane) to give the title as a colorless glass. MS (ESI pos. ion) m/z: 240.4 (M+H). Calc'd Exact Mass for C12H14FNO3: 239.24.
Workup
- customThe white precipitate was removed by filtration
- temperatureThe filtrate was cooled to 0° C.
- waitAfter 1 h
- customThe organic phase was separated
- washwashed with 30 mL of brine
- dry with materialdried over Na2SO4
- concentrationconcentrated in vacuo
- customThe residue was chromatographed by a silica gel column (5% to 80% EtOAc/hexane)
- customto give the title as a colorless glass
Sources & evidence
- ORD record
- ord-fb8e537b659545f680c12b2043c6dccd
- Source dataset
- uspto-grants-2010_01
- Patent number
- US07652009B2
Reaction notes
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