Diethyl Ether → (4-Chloro-3-fluoro-2-methoxyphenyl)[2-(trifluoromethyl)oxiranyl]methanone

HRID 1945124Notes

Reaction equation

HRID 1945124 reaction equation
[F:1][C:2]([F:7])([F:6])[CH:3]1[O:5][CH2:4]1.C([Li])CCC.[Cl:13][C:14]1[CH:25]=[CH:24][C:17]([C:18](N(OC)C)=[O:19])=[C:16]([O:26][CH3:27])[C:15]=1[F:28].C(OCC)C>C1COCC1.CCCCCC>[Cl:13][C:14]1[CH:25]=[CH:24][C:17]([C:18]([C:3]2([C:2]([F:7])([F:6])[F:1])[CH2:4][O:5]2)=[O:19])=[C:16]([O:26][CH3:27])[C:15]=1[F:28]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 5207692-(Trifluoromethyl)oxiraneHCID 866305624-chloro-3-fluoro-2,N-dimethoxy-N-methylbenzamidHCID 178418339Butyllithium

Product 1

HCID 86630563(4-Chloro-3-fluoro-2-methoxyphenyl)[2-(trifluoromethyl)oxiranyl]methanoneYield 83%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent2×

Procedure

0.44 ml (5.1 mmol) 1,1,1-trifluoro-2,3-epoxypropane in 7.5 ml THF and 2.2 ml hexane are cooled to −100° C. and 2.03 ml of a 2.5 M n-butyl lithium solution (5.1 mmol) in hexane are added over 15 minutes while the temperature does not exceed −95° C. 10 minutes after complete addition 0.57 g (2.3 mmol) 4-chloro-3-fluoro-2,N-dimethoxy-N-methylbenzamid in 10 ml THF are added over 15 minutes while the temperature does not exceed −95° C. After 3 hours at −100° C. 2.3 ml diethyl ether is added and the reaction mixture is warmed to room temperature over 14 hours. The reaction is quenched by addition of saturated ammonium chloride solution. The phases were separated and the aqueous layer is extracted twice with diethyl ether, the combined organic phases washed with brine, dried over sodium sulphate and then evaporated to yield 570 mg of (4-chloro-3-fluoro-2-methoxyphenyl)[2-(trifluoromethyl)oxiranyl]methanone. 1H-NMR (CDCl3); δ=2.99 (dq, 1H), 3.37 (d, 1H), 4.14 (d, 3H), 7.18 (m, 1H), 7.19 (m, 1H).

Workup

  1. customdoes not exceed −95° C
  2. additionare added over 15 minutes while the temperature
  3. customdoes not exceed −95° C
  4. customThe reaction is quenched by addition of saturated ammonium chloride solution
  5. customThe phases were separated
  6. extractionthe aqueous layer is extracted twice with diethyl ether
  7. washthe combined organic phases washed with brine
  8. dry with materialdried over sodium sulphate
  9. customevaporated

Sources & evidence

ORD record
ord-6f0a3fbef3d240b3b0e8dce279747ea6
Source dataset
uspto-grants-2013_03
Patent number
US08394958B2

Reaction notes

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