Hexane → (4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

HRID 1874305

Reaction equation

Br[C:2]1[CH:7]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:5]=[C:4]([F:15])[CH:3]=1.[F:16][C:17]1[CH:28]=[CH:27][C:20]([C:21](N(OC)C)=[O:22])=[CH:19][C:18]=1[O:29][CH:30]([CH3:32])[CH3:31].[Li]CCCC.CCCCCC>C1COCC1>[F:16][C:17]1[CH:28]=[CH:27][C:20]([C:21]([C:2]2[CH:7]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:5]=[C:4]([F:15])[CH:3]=2)=[O:22])=[CH:19][C:18]=1[O:29][CH:30]([CH3:32])[CH3:31]

Participants

Conditions

Temperature: -76 °C

Procedure

A 3-liter four neck round-bottomed flask (flame dried) was charged 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (72.88 g, 0.25 mol), 4-fluoro-3-isopropoxy-N-methoxy-N-methylbenzamide (60.39 g, 0.25 mol) and dry THF (700 mL) under N2. The solution was cooled to −76° C., and a solution of n-BuLi in hexane (2.5M, 100 mL, 0.25 mol) was drop-wise maintaining the reaction mixture temperature below −70° C. over a period of 40 min. The reaction mixture was stirred at −76° C. for 1.5 h then quenched with 1N HCl (500 mL). The mixture was concentrated in vacuo to half the volume and was partitioned between EtOAc and H2O (v/v 1:0.3, 1 L). The organic phase was separated and the aqueous layer was extracted with EtOAc (500 mL). The combined organic extracts were washed with brine and then concentrated in vacuo to give a yellow oil which was purified by column chromatography using CH2Cl2 in hexanes (0% to 20%) to give (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as a colorless oil contaminated with a by-product (49.0 g, 50%). LC-MS (10-90% MeOH in H2O with 0.1% TFA in a 2-min gradient) 393.2 (M+H), retention time=2.15 min.

Workup

customthen quenched with 1N HCl (500 mL)
concentrationThe mixture was concentrated in vacuo to half the volume
customwas partitioned between EtOAc and H2O (v/v 1:0.3, 1 L)
customThe organic phase was separated
extractionthe aqueous layer was extracted with EtOAc (500 mL)
washThe combined organic extracts were washed with brine
concentrationconcentrated in vacuo
customto give a yellow oil which
customwas purified by column chromatography

Sources & evidence

ORD record: ord-a49b0cdbf18948b4aa02d19bfb443f17
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304403B2

Linked notes

Loading…