Triphenylphosphine → N-[(4R,4aR,6R,8aS)-6-cyclopropyl-8a-(2,4-difluorophenyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide
Reaction equation
N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:32]1([C@@H:35]2[O:40][CH2:39][C@@:38]([NH:49][C:50]([NH:52][C:53](=[O:60])[C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[S:51])([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=3[F:48])[C@H:37]([C@@H:61](O)[CH3:62])[CH2:36]2)[CH2:34][CH2:33]1>O1CCCC1>[CH:32]1([C@@H:35]2[O:40][CH2:39][C@:38]3([C:41]4[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=4[F:48])[N:49]=[C:50]([NH:52][C:53](=[O:60])[C:54]4[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=4)[S:51][C@H:61]([CH3:62])[C@@H:37]3[CH2:36]2)[CH2:34][CH2:33]1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Diethyl azodicarboxylate (92 μL, 0.59 mmol) was added to a 0° C. solution of triphenylphosphine (153 mg, 0.583 mmol) in tetrahydrofuran (7 mL), and the mixture was stirred for 10 minutes in the ice bath. A solution of N-({(3S,4R,6R)-6-cyclopropyl-3-(2,4-difluorophenyl)-4-[(1S)-1-hydroxyethyl]tetrahydro-2H-pyran-3-yl}carbamothioyl)benzamide (C30) (90 mg, 0.20 mmol) in tetrahydrofuran (2 mL) was added drop-wise to the reaction mixture, which was then stirred for 1 hour under ice cooling. The reaction mixture was concentrated in vacuo; purification via silica gel chromatography (Gradient: 0% to 80% ethyl acetate in heptane) afforded the product as a gum. Yield: 45 mg, 0.10 mmol, 50%. LCMS m/z 441.1 [M−H+].
Workup
- concentrationThe reaction mixture was concentrated in vacuo
- custompurification via silica gel chromatography (Gradient: 0% to 80% ethyl acetate in heptane)
Sources & evidence
- ORD record
- ord-aa07ef9cafcb4d1ca4de7863ebd64d1a
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09403846B2
Reaction notes
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