HCID 86722457, compound → HCID 86722454, compound

HRID 718845Notes

Reaction equation

HRID 718845 reaction equation
[Br:1][C:2]1[C:10]2[N:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:8]=[CH:7][C:6]=2[CH:5]=[C:4]2[C@@:18]3([CH:32]=[CH2:33])[CH2:26][CH2:25][C@:24]([C:28]([F:31])([F:30])[F:29])([OH:27])[CH2:23][C@@H:19]3[CH2:20][CH2:21][O:22][C:3]=12.[Br:34][C:35]1[C:43]2[N:42]([C:44]3[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=3)[N:41]=[CH:40][C:39]=2[CH:38]=[C:37]2[C@:51]3([CH:65]=[CH2:66])[CH2:59][CH2:58][C@@:57]([C:61]([F:64])([F:63])[F:62])([OH:60])[CH2:56][C@H:52]3[CH2:53][CH2:54][O:55][C:36]=12>[Pd].C1COCC1>[Br:1][C:2]1[C:10]2[N:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[N:8]=[CH:7][C:6]=2[CH:5]=[C:4]2[C@@:18]3([CH2:32][CH3:33])[CH2:26][CH2:25][C@:24]([C:28]([F:29])([F:31])[F:30])([OH:27])[CH2:23][C@@H:19]3[CH2:20][CH2:21][O:22][C:3]=12.[Br:34][C:35]1[C:43]2[N:42]([C:44]3[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=3)[N:41]=[CH:40][C:39]=2[CH:38]=[C:37]2[C@:51]3([CH2:65][CH3:66])[CH2:59][CH2:58][C@@:57]([C:61]([F:62])([F:64])[F:63])([OH:60])[CH2:56][C@H:52]3[CH2:53][CH2:54][O:55][C:36]=12

Participants

4

Reactant 1

HCID 86722457HCID 86722457, compound

Product 1

HCID 86722454HCID 86722454, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To 10% Pd/C (wet, 0.162 g) was added a solution of (3R,4aR,12bS)-8-bromo-9-(4-fluorophenyl)-3-(trifluoromethyl)-12b-vinyl-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazol-3-ol; compound with (3S,4aS,12bR)-8-bromo-9-(4-fluorophenyl)-3-(trifluoromethyl)-12b-vinyl-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazol-3-ol (107, R1=4-Fluorophenyl, R2=Vinyl, R3=Trifluoromethyl) (0.443 g, 0.843 mmol) and THF (8.0 mL). The mixture was placed under an hydrogen atmosphere using a balloon. After about 4 h, the hydrogen atmosphere was evacuated and the mixture was filtered through Celite® rinsing with THF (50 mL). The volatiles were removed under reduced pressure. The residue was purified on silica gel (24 g) using a gradient of 0-5% EtOAc in DCM. The fractions containing the product were combined and concentrated under reduced pressure to afford (3R,4aR,12bR)-8-bromo-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazol-3-ol; compound with (3S,4aS,12bS)-8-bromo-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazol-3-ol (108, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.410 g, 92% yield) as an ivory solid. LC/MS, method 3, Rt=2.63 min, MS m/z 527 and 529 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.29 (s, 1H), 7.81 (s, 1H), 7.58-7.51 (m, 2H), 7.39-7.29 (m, 2H), 5.92 (s, 1H), 4.47-4.38 (m, 1H), 3.48-3.38 (m, 1H), 2.41-2.28 (m, 1H), 2.25-1.51 (m, 10H), 0.41 (t, J=7.3 Hz, 3H).

Workup

  1. customthe hydrogen atmosphere was evacuated
  2. filtrationthe mixture was filtered through Celite®
  3. washrinsing with THF (50 mL)
  4. customThe volatiles were removed under reduced pressure
  5. customThe residue was purified on silica gel (24 g)
  6. additionThe fractions containing the product
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d6b6e85256e34356be96850c5d4740ca
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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