Bromobenzene → (2R)-4-Biphenyl-4-yl-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533541Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[CH3:7][C@@:8]([S:36]([CH3:39])(=[O:38])=[O:37])([CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=1)[C:9]([NH:11][O:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][O:14]1)=[O:10].Br[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>COCCOC.CO.C(OCC)(=O)C>[C:24]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:23]=[CH:22][C:21]([CH2:20][CH2:19][C@@:8]([CH3:7])([S:36]([CH3:39])(=[O:38])=[O:37])[C:9]([NH:11][O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)=[O:10])=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Trisdibenzylidine dipalladium (0.19 g, 0.21 mmol) was added to a mixture of potassium carbonate (1.45 g, 10.5 mmol, 5.0 equiv), (2R)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]butanamide, which may be prepared as in Preparation 8C (1.0 g, 2.1 mmol) and bromobenzene (0.26 mL, 2.5 mmol) in 1,2-dimethoxyethane-methanol (8.0 mL, 1:1). The reaction was heated to 80° C. and allowed to stir overnight. The reaction was diluted with ethyl acetate (60 mL), filtered through a pad of Celite, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (heptane/ethyl acetate system) to provide the title compound as a tan gum-like material (72 mg, 8%). MS (LCMS) m/z 430.8 (M−1).

Workup

filtrationfiltered through a pad of Celite
concentrationconcentrated under reduced pressure
customThe crude material was purified by flash chromatography on silica gel (heptane/ethyl acetate system)

Sources & evidence

ORD record: ord-45f0f224d2cc451e9f4cb5359bbdf7d7
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853258B2

Reaction notes

Loading…