Triacetoxyperiodinane → HCID 86722399, compound

HRID 718800Notes

Reaction equation

HRID 718800 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([C@@:25]12[CH2:50][CH2:49][C@@:48]([C:52]([F:55])([F:54])[F:53])([OH:51])[CH2:47][C@H:26]1[CH2:27][CH2:28][C@H:29]([OH:46])[C:30]1[C:31]2=[CH:32][C:33]2[CH:34]=[N:35][N:36]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)[C:37]=2[CH:38]=1)[CH3:24].C([C@@]12CC[C@@](C(F)(F)F)(O)C[C@H]1CC[C@@H](O)C1C2=CC2C=NN(C3C=CC(F)=CC=3)C=2C=1)C.C([O-])(O)=O.[Na+]>CC#N.O.C(Cl)Cl>[CH2:23]([C@@:25]12[CH2:50][CH2:49][C@:48]([OH:51])([C:52]([F:55])([F:53])[F:54])[CH2:47][C@H:26]1[CH2:27][CH2:28][C:29](=[O:46])[C:30]1[C:31]2=[CH:32][C:33]2[CH:34]=[N:35][N:36]([C:39]3[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=3)[C:37]=2[CH:38]=1)[CH3:24]

Participants

8

Reactant 4

HCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 86722398HCID 86722398, compoundHCID 86722400HCID 86722400, compound

Product 1

HCID 86722399HCID 86722399, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Dess-Martin periodinane (0.017 g, 0.039 mmol) was added to a solution of (3R,4aR,7 S,12bR)-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-3,7-diol (61, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.0079 g, 0.017 mmol), (3R,4aR,7R,12bR)-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-3,7-diol (62, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.0061 g, 0.013 mmol), and DCM (0.300 mL) under a nitrogen atmosphere. After about 90 min, sat. aq. NaHCO3 (2 mL) and water (1 mL) were added. The mixture was extracted with EtOAc (2×5 mL). The combined organics were dried over Na2SO4, filtered, and concentrated. The residue was purified on silica gel (4 g) using a gradient of 0-25% EtOAc in heptane. The fractions containing product were combined and concentrated under reduced pressure to afford an ivory foam. The residue was dissolved in MeCN, treated with water, and concentrated under reduced pressure to remove MeCN. The mixture was frozen then lyophilized to afford (3R,4aR,12bR)-12b-ethyl-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-7(9H)-one (63, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.0124 g, 89% yield) of an ivory solid. LC/MS, method 2, Rt=2.54 min, MS m/z 461 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.41-8.38 (m, 1H), 7.93 (s, 1H), 7.84-7.75 (m, 2H), 7.54 (s, 1H), 7.48-7.39 (m, 2H), 5.94 (s, 1H), 2.86-2.74 (m, 1H), 2.70-2.59 (m, 1H), 2.26-2.14 (m, 1H), 2.09-1.84 (m, 5H), 1.81-1.59 (m, 4H), 1.54-1.40 (m, 1H), 0.37 (t, J=7.2 Hz, 3H).

Workup

  1. extractionThe mixture was extracted with EtOAc (2×5 mL)
  2. dry with materialThe combined organics were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel (4 g)
  6. additionThe fractions containing product
  7. concentrationconcentrated under reduced pressure
  8. customto afford an ivory foam
  9. concentrationconcentrated under reduced pressure
  10. customto remove MeCN
  11. temperatureThe mixture was frozen

Sources & evidence

ORD record
ord-11b7a3e6743b49929b0ffa4b46df04b3
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

Loading…