Ammonia → rac-(4aR,12bS)-12b-ethyl-1,2,4,4a,5,6,9,12b-octahydrospiro[benzo[4,5]oxepino[3,2-f]indazole-3,2'-[1,3]dioxolane]

HRID 718831Notes

Reaction equation

HRID 718831 reaction equation
[CH2:1]([C@:3]12[CH2:27][CH2:26][C:21]3([O:25][CH2:24][CH2:23][O:22]3)[CH2:20][C@H:4]1[CH2:5][CH2:6][O:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:12]=[N:13][N:14](C(=O)C)[C:15]=2[CH:16]=1)[CH3:2].N>C1COCC1.CO>[CH2:1]([C:3]12[CH2:27][CH2:26][C:21]3([O:25][CH2:24][CH2:23][O:22]3)[CH2:20][CH:4]1[CH2:5][CH2:6][O:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:12]=[N:13][NH:14][C:15]=2[CH:16]=1)[CH3:2]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 90003780rac-1-((4aR,12bS)-12b-ethyl-1,4,4a,5,6,12b-hexahydrospiro[benzo[4,5]oxepino[3,2-f]indazole-3,2'-[1,3]dioxolan]-9(2H)-yl)ethanone

Product 1

HCID 86722439rac-(4aR,12bS)-12b-ethyl-1,2,4,4a,5,6,9,12b-octahydrospiro[benzo[4,5]oxepino[3,2-f]indazole-3,2'-[1,3]dioxolane]Yield 100.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of rac-1-((4aR,12bS)-12b-ethyl-1,4,4a,5,6,12b-hexahydro spiro[benzo[4,5]oxepino[3,2-f]indazole-3,2′-[1,3]dioxolan]-9(2H)-yl)ethanone (89, R2=Ethyl) (3.02 g, 8.15 mmol) in a mixture of THF (54 mL) and MeOH (27 mL) was treated with ammonia (7 M in MeOH, 3.49 mL, 24.5 mmol) and stirred at rt overnight. The reaction mixture was concentrated under reduced pressure to give rac-(4aR,12bS)-12b-ethyl-1,2,4,4a,5,6,9,12b-octahydrospiro[benzo[4,5]oxepino[3,2-f]indazole-3,2′-[1,3]dioxolane] (90, R2=Ethyl) (2.68 g, 100%). The material was used without further purification. LC/MS, method 3, 2.09 min, MS m/z 329 (M+1)+. 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.57 (s, 1H), 7.07 (s, 1H), 4.33-4.24 (m, 1H), 4.00-3.84 (m, 4H), 3.75-3.64 (m, 1H), 2.79-2.66 (m, 1H), 2.51-2.40 (m, 1H), 2.33-2.19 (m, 2H), 2.09-1.98 (m, 1H), 1.88-1.78 (m, 1H), 1.76-1.29 (m, 5H), (t, J=7.5 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-11e6d49f0c8247c1ac62b93f4a779281
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

Loading…