Water → 2-(2-Fluoro-4-methylbenzoyl)cyclopropanecarbonitrile

HRID 561455Notes

Reaction equation

HRID 561455 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][C:8]=1[F:14].[C:15]([CH:17]1[CH2:19][CH:18]1[C:20](N(OC)C)=[O:21])#[N:16].O>CCCCCC.C1COCC1>[F:14][C:8]1[CH:9]=[C:10]([CH3:13])[CH:11]=[CH:12][C:7]=1[C:20]([CH:18]1[CH2:19][CH:17]1[C:15]#[N:16])=[O:21]

Participants

7

Reactant 4

HCID 962WaterHCID 5732804-Bromo-3-fluorotolueneHCID 583925062-Cyano-N-methoxy-N-methylcyclopropanecarboxamideHCID 178418339Butyllithium

Product 1

HCID 583925332-(2-Fluoro-4-methylbenzoyl)cyclopropanecarbonitrile

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

16.5 ml (26.5 mmol) of a 1.6N solution of n-butyllithium in hexane were added dropwise to a solution of 5.00 g (26.5 mmol) of 4-bromo-3-fluorotoluene in 40 ml of THF at −78° C., and the mixture was stirred for 0.5 h. Then, at −78° C., a solution of 2.72 g (17.6 mmol) of the compound from Example 73A in 10 ml of THF was added, and the mixture was allowed to warm to RT and was stirred at RT for 2 h. Water was added, the mixture was concentrated, and the crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid). 300 mg (9% of theory) of the title compound were obtained.

Workup

  1. stirringwas stirred at RT for 2 h
  2. concentrationthe mixture was concentrated
  3. customthe crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record
ord-0ac766767f7740a0b719c35b91e833ff
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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