Water → HCID 86709993, compound

HRID 920632Notes

Reaction equation

HRID 920632 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([C:21](OC)=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:25]([C:28]2[CH:33]=[C:32]([F:34])[C:31]([F:35])=[C:30]([F:36])[CH:29]=2)(=[O:27])=[O:26])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1.[H-].C([Al+]CC(C)C)C(C)C.O>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([CH2:21][OH:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:25]([C:28]2[CH:29]=[C:30]([F:36])[C:31]([F:35])=[C:32]([F:34])[CH:33]=2)(=[O:27])=[O:26])[CH2:16][CH2:15]4)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 21225700DiisobutylaluminumhydrideHCID 86709994HCID 86709994, compound

Product 1

HCID 86709993HCID 86709993, compoundYield 71.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (R)-methyl 1-(4-fluorophenyl)-6-((3,4,5-trifluorophenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinoline-4a-carboxylate (1.0 g, 1.918 mmol) in anhydrous dichloromethane (30 mL) at −78° C. under a nitrogen atmosphere was added diisobutyl aluminium hydride (DIBAL-H) (1 M in Heptane) (7.67 ml, 7.67 mmol) dropwise over 10 minutes. The reaction mixture was stirred at −78° C. for 1 hour. Water (10 mL) was then added and the reaction mixture stirred at −78° C. for 5 minutes, then warmed to room temperature over 15 minutes. The solution was partitioned between ethyl acetate (150 mL) and Rochelle's salt (150 mL). The organic layer was washed with Rochelle's salt (150 mL), brine (100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to give an off white solid. The crude product was purified by chromatography on silica gel (gradient: 0-90% ethyl acetate in isohexane) to afford (R)-(1-(4-fluorophenyl)-6-((3,4,5-trifluorophenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)methanol (680 mg) as a white solid. LCMS (Method F, ES-API): RT 2.58 min, m+H=494.2.

Workup

  1. stirringthe reaction mixture stirred at −78° C. for 5 minutes
  2. temperaturewarmed to room temperature over 15 minutes
  3. customThe solution was partitioned between ethyl acetate (150 mL) and Rochelle's salt (150 mL)
  4. washThe organic layer was washed with Rochelle's salt (150 mL), brine (100 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give an off white solid
  9. customThe crude product was purified by chromatography on silica gel (gradient: 0-90% ethyl acetate in isohexane)

Sources & evidence

ORD record
ord-e9c1ba424e934d3fa136795e874390de
Source dataset
uspto-grants-2016_03
Patent number
US09273047B2

Reaction notes

Loading…