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

HRID 1478739Notes

Reaction equation

HRID 1478739 reaction equation
[CH:1]1([C@@H:4]2[O:14][CH2:13][C:7]3=[N:8][O:9][C@@H:10]([CH2:11][F:12])[C@@H:6]3[CH2:5]2)[CH2:3][CH2:2]1.C1([C@@H]2OC[C@]3([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=4[F:34])NOC[C@@H]3C2)CC1>>[CH:1]1([C@@H:4]2[O:14][CH2:13][C@:7]3([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=4[F:34])[NH:8][O:9][C@@H:10]([CH2:11][F:12])[C@@H:6]3[CH2:5]2)[CH2:2][CH2:3]1

Participants

3

Reactant 2

HCID 90253447rel-(3R,3aR,5R)-5-cyclopropyl-3-(fluoromethyl)-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazoleHCID 118621161HCID 118621161, compound

Product 1

HCID 90253440rel-(3R,3aR,5R,7aS)-5-cyclopropyl-7a-(2,4-difluorophenyl)-3-(fluoromethyl)hexahydro-1H-pyrano[3,4-c][1,2]oxazole

Procedure

Conversion of rel-(3R,3aR,5R)-5-cyclopropyl-3-(fluoromethyl)-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole (C43) to the product was carried out using 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 an oil. Yield: 0.10 g, 0.32 mmol, 64%. 1H NMR (400 MHz, CDCl3) δ 7.93 (ddd, J=9, 9, 7 Hz, 1H), 6.90 (br ddd, J=9, 8, 2 Hz, 1H), 6.80 (ddd, J=12, 8.6, 2.5 Hz, 1H), 6.45 (s, 1H), 4.12-4.21 (m, 1H), 3.60-3.95 (m, 4H), 3.09 (br dd, J=9, 9 Hz, 1H), 2.88 (br dd, J=10, 9 Hz, 1H), 2.18 (br dd, J=14, 7.5 Hz, 1H), 1.63-1.75 (m, 1H), 0.88-0.98 (m, 1H), 0.52-0.64 (m, 2H), 0.37-0.46 (m, 1H), 0.24-0.33 (m, 1H).

Workup

  1. customThe product was obtained as an oil

Sources & evidence

ORD record
ord-e5554d8f9df54b97a36ee88aae0e1289
Source dataset
uspto-grants-2016_08
Patent number
US09403846B2

Reaction notes

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