3,3-Difluoroazetidine hydrochloride → 1-{3-Chloro-6-[2-(3,3-difluoro-azetidin-1-yl)-ethoxy]-5-[3-(4-fluoro-phenyl)-butoxy]-4-methoxy-2-methyl-phenyl}-ethanone

HRID 219463

Reaction equation

HRID 219463 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[C:10]([O:11][CH2:12][CH2:13][CH:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH3:15])=[C:9]([O:23][CH3:24])[C:8]([Cl:25])=[C:7]([CH3:26])[C:6]=1[C:27](=[O:29])[CH3:28].Cl.[F:31][C:32]1([F:36])[CH2:35][NH:34][CH2:33]1>>[Cl:25][C:8]1[C:7]([CH3:26])=[C:6]([C:27](=[O:29])[CH3:28])[C:5]([O:4][CH2:3][CH2:2][N:34]2[CH2:35][C:32]([F:36])([F:31])[CH2:33]2)=[C:10]([O:11][CH2:12][CH2:13][CH:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH3:15])[C:9]=1[O:23][CH3:24]

Participants

3

Reactant 2

HCID 27582473,3-Difluoroazetidine hydrochlorideHCID 595835231-{2-(2-Bromo-ethoxy)-5-chloro-3-[3-(4-fluoro-phenyl)-butoxy]-4-methoxy-6-methyl-phenyl}-ethanone

Product 1

HCID 252546851-{3-Chloro-6-[2-(3,3-difluoro-azetidin-1-yl)-ethoxy]-5-[3-(4-fluoro-phenyl)-butoxy]-4-methoxy-2-methyl-phenyl}-ethanoneYield 37%

Procedure

Example 8a (102 mg, 0.21 mmol) was reacted with 3,3-difluoroazetidine hydrochloride (2.6 eq.) as described under General Procedure K and the crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 60:40) to afford the title compound as a pale yellow oil (39 mg, 37%). 1H NMR (300 MHz, CDCl3) δ7.20-7.17 (m, 2H), 7.01-6.95 (m, 2H), 3.98-3.91 (m, 4H), 3.83 (s, 3H), 3.62 (t, J=12.0 Hz, 4H), 2.99 (m, 1H), 2.80 (t, J=5.6 Hz, 2H), 2.50 (s, 3H), 2.18 (s, 3H), 2.07-2.01 (m, 2H), 1.30 (d J=6.9 Hz, 3H). MS (ES+) m/z 500.1 (M+H+).

Workup

  1. customthe crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 60:40)

Sources & evidence

ORD record
ord-7531763000634de8abfa2f4f80f9dc04
Source dataset
uspto-grants-2012_06
Patent number
US08202513B2

Linked notes

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