Water → HCID 74221306, compound

HRID 718869Notes

Reaction equation

HRID 718869 reaction equation
[CH2:1]([C@@:3]12[CH2:28][CH2:27][C@@:26]([C:30]([F:33])([F:32])[F:31])([OH:29])[CH2:25][C@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:12]=[N:13][N:14]([C:17]3[CH:22]=[CH:21][C:20]([S:23][CH3:24])=[CH:19][CH:18]=3)[C:15]=2[CH:16]=1)[CH3:2].[OH2:34].ClC1C=C(C=CC=1)C(OO)=[O:40]>CC(C)=O>[CH2:1]([C@@:3]12[CH2:28][CH2:27][C@@:26]([C:30]([F:33])([F:32])[F:31])([OH:29])[CH2:25][C@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:12]=[N:13][N:14]([C:17]3[CH:18]=[CH:19][C:20]([S:23]([CH3:24])(=[O:40])=[O:34])=[CH:21][CH:22]=3)[C:15]=2[CH:16]=1)[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 70297m-Chloroperbenzoic acidHCID 86722485HCID 86722485, compound

Product 1

HCID 74221306HCID 74221306, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

(3R,4aR,12bR)-12b-Ethyl-9-(4-(methylthio)phenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (11, R1=4-(Methylthio)phenyl, R2=Ethyl, R3=Trifluoromethyl) (230 mg, 0.485 mmol) in acetone (10 mL) and water (2 mL) was treated with 3-chlorobenzoperoxoic acid (543 mg, 2.42 mmol) at rt. After 30 min the mixture was concentrated under reduced pressure then the material was partitioned between sat. aq. NaHCO3 (15 mL), water (15 mL) and EtOAc (30 mL). The organic layer was washed with brine (10 mL), dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure then the material was purified on silica gel (12 g) using 0-40% EtOAc in DCM. Product fractions were concentrated under reduced pressure then triturated with Et2O (1.5 mL) in heptane (20 mL). The solids were collected by filtration and dried to yield (3R,4aR,12bR)-12b-ethyl-9-(4-(methylsulfonyl)phenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (11, R1=4-(Methylsulfonyl)phenyl, R2=Ethyl, R3=Trifluoromethyl) (110.6 mg, 45.0%); LC/MS, method 2, Rt=2.43 min, MS m/z 507 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.37 (d, J=0.8 Hz, 1H), 8.14-8.06 (m, 4H), 7.88 (s, 1H), 7.80 (s, 1H), 5.86 (s, 1H), 3.30 (s, 3H), 3.28-3.22 (m, 1H), 3.02-2.97 (m, 1H), 2.29-2.20 (m, 1H), 2.16-1.98 (m, 4H), 1.93-1.75 (m, 2H), 1.73-1.54 (m, 5H), 1.41-1.30 (m, 1H), 0.44 (t, J=7.3 Hz, 3H).

Workup

  1. concentrationAfter 30 min the mixture was concentrated under reduced pressure
  2. customthe material was partitioned between sat. aq. NaHCO3 (15 mL), water (15 mL) and EtOAc (30 mL)
  3. washThe organic layer was washed with brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe material was purified on silica gel (12 g)
  8. concentrationProduct fractions were concentrated under reduced pressure
  9. customthen triturated with Et2O (1.5 mL) in heptane (20 mL)
  10. filtrationThe solids were collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-3fd60bec81c64ff5a906ca93f952c96d
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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