Hydrochloric Acid → Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoate

HRID 1183753Notes

Reaction equation

[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:7]=[C:8]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[C:9]=1[O:10][CH2:11][CH:12]1[CH2:14][CH2:13]1.[F:31][C:32]([F:36])([F:35])[CH2:33]I.Cl>CN(C=O)C.O>[Cl:3][C:4]1[CH:5]=[C:6]([CH:25]([CH2:33][C:32]([F:36])([F:35])[F:31])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:7]=[C:8]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:19][CH:20]=2)[C:9]=1[O:10][CH2:11][CH:12]1[CH2:13][CH2:14]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of NaH (64 mg, 0.13 mmol) in DMF (15 mL) was added ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (500 mg, 0.12 mmol) and 1,1,1-trifluoro-2-iodoethane (0.304 mL, 0.15 mmol) at 0° C. The reaction mixture was stirred at 0° C. over a period of 30 min. After completion of starting material (by TLC), diluted with water (20 mL), acidified with 1N HCl (pH=5) and extracted with EtOAc (3×30 mL). Combined organic layers were washed with water (3×15 mL), brine and dried over anhydrous Na2SO4. After filtration and evaporation, the crude material was purified by column chromatography to afford ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoate (300 mg) as liquid.

Workup

extractionextracted with EtOAc (3×30 mL)
washCombined organic layers were washed with water (3×15 mL), brine
dry with materialdried over anhydrous Na2SO4
filtrationAfter filtration and evaporation
customthe crude material was purified by column chromatography

Sources & evidence

ORD record: ord-91a890a14855439ab1b6e0840f3e8511
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08664249B2

Reaction notes

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