(3aR,5R,7aS)-7a-(5-bromo-2-fluorophenyl)-5-cyclopropylhexahydro-1H-pyrano[3,4-c][1,2]oxazole → [(2R,4R,5S)-5-amino-5-(5-bromo-2-fluorophenyl)-2-cyclopropyltetrahydro-2H-pyran-4-yl]methanol
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C@:8]23[CH2:16][O:15][C@@H:14]([CH:17]4[CH2:19][CH2:18]4)[CH2:13][C@H:12]2[CH2:11][O:10][NH:9]3)[CH:7]=1>C(O)(=O)C.[Zn]>[NH2:9][C@@:8]1([C:6]2[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[F:20])[CH2:16][O:15][C@@H:14]([CH:17]2[CH2:18][CH2:19]2)[CH2:13][C@H:12]1[CH2:11][OH:10]Participants
4
Reactant 1
Product 1
Reagents, catalysts & solvents 2
Procedure
Zinc dust (1.06 g, 16.2 mmol) was added to a solution of (3aR,5R,7aS)-7a-(5-bromo-2-fluorophenyl)-5-cyclopropylhexahydro-1H-pyrano[3,4-c][1,2]oxazole (C55) (311 mg, 1.08 mmol) in acetic acid (56 mL). The reaction mixture was allowed to stir at room temperature overnight. The reaction was filtered through an empty Bakerbond cartridge, eluting with ethyl acetate to remove the zinc. The filtrate was concentrated and then passed through a 4 g methanol-conditioned MCX cartridge. This was washed with methanol (4×15 mL), dichloromethane (4×15 mL) and 2 N ammonia in methanol (40 mL). The filtrate was concentrated in vacuo to give the product (225 mg), which was taken directly to the following step. LCMS m/z 291.2 [M+H+].
Workup
- filtrationThe reaction was filtered through an empty Bakerbond cartridge
- washeluting with ethyl acetate
- customto remove the zinc
- concentrationThe filtrate was concentrated
- washThis was washed with methanol (4×15 mL), dichloromethane (4×15 mL) and 2 N ammonia in methanol (40 mL)
- concentrationThe filtrate was concentrated in vacuo
Sources & evidence
- ORD record
- ord-a9c30ba5118d4c4ebc11ac5fa71028ac
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08822456B2
Reaction notes
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