2-Methyl-2-butene → HCID 86722383, compound

HRID 718786Notes

Reaction equation

HRID 718786 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][CH:20]5[CH2:25][C:24]([O:30][Si:31]([CH2:36][CH3:37])([CH2:34][CH3:35])[CH2:32][CH3:33])([C:26]([F:29])([F:28])[F:27])[CH2:23][CH2:22][C:21]5([CH:38]=[O:39])[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.P([O-])(O)(O)=[O:41].[Na+].CC(=CC)C.Cl([O-])=O.[Na+]>O.C(O)(C)(C)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][CH:20]5[CH2:25][C:24]([O:30][Si:31]([CH2:36][CH3:37])([CH2:32][CH3:33])[CH2:34][CH3:35])([C:26]([F:29])([F:27])[F:28])[CH2:23][CH2:22][C:21]5([C:38]([OH:41])=[O:39])[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86722384HCID 86722384, compound

Product 1

HCID 86722383HCID 86722383, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

t-Butanol (20 mL) and water (4 mL) were added to rac-(3R,4aR,12bS)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carb aldehyde (40, R1=4-Fluorophenyl, R3=Trifluoromethyl) (0.360 g, 0.642 mmol). After cooling to about 0° C., sodium dihydrogenphosphate (0.770 g, 6.42 mmol), 2-methyl-but-2-ene (0.270 g, 3.85 mmol), and sodium chlorite (0.348 g, 3.85 mmol) were added sequentially. After about 30 min, the ice bath was removed and the reaction was allowed to warm to rt. After about 3 h, a 1:1 solution of sat. aq. Na2SO3 and sat. aq. NaCl (50 mL) was added. Water (30 mL) was added. The mixture was extracted with EtOAc (3×50 mL). The combined organics were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (40 g) using a gradient of 0-20% EtOAc in heptane. The product fractions were combined and concentrated under reduced pressure to give rac-(3R,4aR,12bS)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carboxylic acid (43, R1=4-Fluorophenyl, R3=Trifluoromethyl) (0.267 g, 72% yield); LC/MS, method 4, Rt=2.39 min.; MS m/z: 577 (M+H)+. 1H NMR (400 MHz, DMSO) δ 12.57 (s, 1H), 8.26 (d, J=0.7 Hz, 1H), 7.90 (s, 1H), 7.82-7.75 (m, 2H), 7.54 (s, 1H), 7.45-7.35 (m, 2H), 2.95-2.71 (m, 2H), 2.60-2.48 (m, 1H), 2.42-2.15 (m, 4H), 2.03-1.78 (m, 3H), 1.73-1.52 (m, 2H), 1.34-1.20 (m, 1H), 0.99-0.90 (m, 9H), 0.69-0.59 (m, 6H).

Workup

  1. customthe ice bath was removed
  2. temperatureto warm to rt
  3. waitAfter about 3 h
  4. additiona 1:1 solution of sat. aq. Na2SO3 and sat. aq. NaCl (50 mL) was added
  5. additionWater (30 mL) was added
  6. extractionThe mixture was extracted with EtOAc (3×50 mL)
  7. dry with materialThe combined organics were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified on silica gel (40 g)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-dc1ee7ffc0294d9999d3ba1b4ceaba6b
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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