[(2R,4R,5S)-5-amino-2-[(benzyloxy)methyl]-5-(2,4-difluorophenyl)tetrahydro-2H-pyran-4-yl]methanol → rel-[(2R,4R,5S)-5-amino-2-cyclopropyl-5-(2,4-difluorophenyl)tetrahydro-2H-pyran-4-yl]methanol
Reaction equation
[CH:1]1([C@@H:4]2[O:12][CH2:11][C@:7]3([C:13]4[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=4[F:20])[NH:8][O:9][CH2:10][C@@H:6]3[CH2:5]2)[CH2:3][CH2:2]1.N[C@@]1(C2C=CC(F)=CC=2F)CO[C@@H](COCC2C=CC=CC=2)C[C@H]1CO>>[NH2:8][C@@:7]1([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])[CH2:11][O:12][C@@H:4]([CH:1]2[CH2:2][CH2:3]2)[CH2:5][C@H:6]1[CH2:10][OH:9]Participants
Procedure
rel-(3aR,5R,7aS)-5-Cyclopropyl-7a-(2,4-difluorophenyl)hexahydro-1H-pyrano[3,4-c][1,2]oxazole (C19) (1.19 g, 4.23 mmol) was converted to the product according to the method described for the synthesis of [(2R,4R,5S)-5-amino-2-[(benzyloxy)methyl]-5-(2,4-difluorophenyl)tetrahydro-2H-pyran-4-yl]methanol (C6) in Preparation P1. The product was obtained as a thick, pale amber gum (1.22 g), which was taken directly to the following step without additional purification. LCMS m/z 284.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 7.61-7.77 (br m, 1H), 6.90-7.05 (br m, 1H), 6.82 (ddd, J=12.7, 8.6, 2.6 Hz, 1H), 4.13 (dd, J=11.5, 2.5 Hz, 1H), 3.55 (br dd, J=11, 2 Hz, 1H), 3.32-3.49 (br m, 2H), 2.89 (ddd, J=11.3, 8.2, 2.5 Hz, 1H), 2.03-2.34 (br m, 2H), 1.81 (ddd, J=14.0, 4.0, 2.6 Hz, 1H), 1.01-1.13 (br m, 1H), 0.53-0.65 (m, 2H), 0.41-0.48 (m, 1H), 0.24-0.32 (m, 1H).
Sources & evidence
- ORD record
- ord-8a51e2bf171d461f8fcb196d22e4220e
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09403846B2
Reaction notes
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