Sodium borohydride → 1H-Pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8(7H)-butanol, α-(4-fluorophenyl)-2,3,6b,9,10,10a-hexahydro-3-methyl-, (6bR,10aS)-

HRID 880378Notes

Reaction equation

HRID 880378 reaction equation
S(C1C=CC(C)=CC=1)(O)(=O)=O.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:40])[CH2:20][CH2:21][CH2:22][N:23]2[CH2:39][CH2:38][C@@H:26]3[N:27]4[C:36]5[C:35]([C@@H:25]3[CH2:24]2)=[CH:34][CH:33]=[CH:32][C:31]=5[N:30]([CH3:37])[CH2:29][CH2:28]4)=[CH:15][CH:14]=1.[BH4-].[Na+]>CO>[F:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([OH:40])[CH2:20][CH2:21][CH2:22][N:23]2[CH2:39][CH2:38][C@@H:26]3[N:27]4[C:36]5[C:35]([C@@H:25]3[CH2:24]2)=[CH:34][CH:33]=[CH:32][C:31]=5[N:30]([CH3:37])[CH2:29][CH2:28]4)=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 44241743Lumateperone tosylate

Product 1

HCID 545795431H-Pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8(7H)-butanol, α-(4-fluorophenyl)-2,3,6b,9,10,10a-hexahydro-3-methyl-, (6bR,10aS)-Yield 99.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-10 °C

Procedure

1-(4-Fluoro-phenyl)-4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one tosylate salt (8.58 g, 15.2 mmol) is dissolved in 150 mL of methanol. The obtained brown solution is cooled to −10° C., and then NaBH4 (1.72 g, 45.5 mmol) is added slowly. After the addition is complete, the reaction mixture is stirred at room temperature for an hour, and then quenched by adding 20 mL of water. After solvent is removed by rotary evaporation, the residue is treated with 50 mL of 1N NaOH aqueous solution, and then extracted with methylene chloride four times. The combined organic phase is washed with water, dried with anhydrous sodium sulfate, and then evaporated to dryness under vacuum to give 6 g of white foamy solids with 97.8% purity and 99% yield. MS (ESI) m/z 396.1 [M+H]+.

Workup

  1. additionAfter the addition
  2. customquenched
  3. additionby adding 20 mL of water
  4. customAfter solvent is removed by rotary evaporation
  5. additionthe residue is treated with 50 mL of 1N NaOH aqueous solution
  6. extractionextracted with methylene chloride four times
  7. washThe combined organic phase is washed with water
  8. dry with materialdried with anhydrous sodium sulfate
  9. customevaporated to dryness under vacuum

Sources & evidence

ORD record
ord-29b42646f16a4f2a974eae2953124f95
Source dataset
uspto-grants-2015_03
Patent number
US08993572B2

Reaction notes

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