Sodium borohydride → HCID 86722349, compound

HRID 718769Notes

Reaction equation

HRID 718769 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][C@@H:20]5[CH2:27][C@:24]6([CH2:26][O:25]6)[CH2:23][CH2:22][C@:21]5([CH2:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=5)[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[BH4-].[Na+]>CCO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@@H:20]5[CH2:27][C@@:24]([CH3:26])([OH:25])[CH2:23][CH2:22][C@:21]5([CH2:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=5)[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1.[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@H:20]5[CH2:27][C@:24]([CH3:26])([OH:25])[CH2:23][CH2:22][C@@:21]5([CH2:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=5)[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86722352HCID 86722352, compound

Product 1

HCID 86722349HCID 86722349, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of (2′R,4aS,12bS)-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-2,4,4a,5,6,7,9,12b-octahydro-1H-spiro[benzo[6,7]cyclohepta[1,2-f]indazole-3,2′-oxirane]compound with (2′S,4aR,12bR)-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-2,4,4a,5,6,7,9,12b-octahydro-1H-spiro[benzo[6,7]cyclohepta[1,2-f]indazole-3,2′-oxirane] (12, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (500 mg, 1.10 mmol) in EtOH (10 mL) was treated with NaBH4 (104 mg, 2.76 mmol). The reaction was warmed to 60° C. for about 20 min and then allowed to stir at rt for about 18 h. The reaction was concentrated under reduced pressure, then sat. aq. NH4Cl (25 mL) was added and the product was extracted with EtOAc (2×25 mL). The organic solution was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (25 g) using EtOAc as eluent. Product fractions were combined and concentrated to yield (3R,4aS,12bS)-9-(4-fluorophenyl)-3-methyl-12b-(pyridin-2-ylmethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol; compound with (3S,4aR,12bR)-9-(4-fluorophenyl)-3-methyl-12b-(pyridin-2-ylmethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (13, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl, R3=Methyl) (503 mg, 100%) as a white solid.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. additionsat. aq. NH4Cl (25 mL) was added
  3. extractionthe product was extracted with EtOAc (2×25 mL)
  4. dry with materialThe organic solution was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified on silica gel (25 g)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-5544032ff5194e4ab31e4b006d6fcf2c
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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