(3S,3aR,5R)-5-cyclopropyl-3-methyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole → (3S,3aR,5R,7aS)-5-cyclopropyl-7a-(2,4-difluorophenyl)-3-methylhexahydro-1H-pyrano[3,4-c][1,2]oxazole

HRID 1478722Notes

Reaction equation

[CH:1]1([C@@H:4]2[O:13][CH2:12][C:7]3=[N:8][O:9][C@@H:10]([CH3:11])[C@@H:6]3[CH2:5]2)[CH2:3][CH2:2]1.C1([C@@H]2OC[C@]3([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[F:33])NOC[C@@H]3C2)CC1>>[CH:1]1([C@@H:4]2[O:13][CH2:12][C@:7]3([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[F:33])[NH:8][O:9][C@@H:10]([CH3:11])[C@@H:6]3[CH2:5]2)[CH2:2][CH2:3]1

Participants

Reactant 2

HCID 90253543(3S,3aR,5R)-5-cyclopropyl-3-methyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole

HCID 118621161HCID 118621161, compound

Product 1

HCID 90253542(3S,3aR,5R,7aS)-5-cyclopropyl-7a-(2,4-difluorophenyl)-3-methylhexahydro-1H-pyrano[3,4-c][1,2]oxazole

Procedure

(3S,3aR,5R)-5-Cyclopropyl-3-methyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole (C27) was converted to the product according to the method described for synthesis of rel-(3aR,5R,7aS)-5-cyclopropyl-7a-(2,4-difluorophenyl)hexahydro-1H-pyrano[3,4-c][1,2]oxazole (C19) in Example 2. The product was obtained as a gum. Yield: 60 mg, 0.20 mmol, 40%. 1H NMR (400 MHz, CDCl3) δ 7.99 (ddd, J=9.2, 9.0, 6.8 Hz, 1H), 6.90 (dddd, J=8.9, 7.9, 2.6, 1.0 Hz, 1H), 6.79 (ddd, J=11.9, 8.7, 2.5 Hz, 1H), 6.31 (br s, 1H), 4.03-4.10 (m, 1H), 3.89 (dd, half of ABX pattern, J=12.8, 2.0 Hz, 1H), 3.80 (br dd, half of ABX pattern, J=12.8, 1.5 Hz, 1H), 2.79-2.91 (m, 2H), 2.16 (ddd, J=14.3, 7.5, 2.5 Hz, 1H), 1.64 (dddd, J=14.2, 10.7, 10.7, 1.7 Hz, 1H), 0.90-0.99 (m, 1H), 0.79 (d, J=6.5 Hz, 3H), 0.52-0.64 (m, 2H), 0.39-0.45 (m, 1H), 0.24-0.31 (m, 1H).

Workup

customThe product was obtained as a gum

Sources & evidence

ORD record: ord-edd3faa6da4d4cbfbaa19499092d1b1d
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403846B2

Reaction notes

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