Sodium borohydride → HCID 66582823, compound

HRID 1972509Notes

Reaction equation

HRID 1972509 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:27])([CH3:26])[C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[C@@H:11]([CH2:28][N:29]2[CH:34]3[CH2:35][CH2:36][CH2:37][CH:30]2[CH2:31][C:32](=[O:38])[CH2:33]3)[CH2:10]1)(=[O:8])=[O:7].[BH4-].[Na+]>C1COCC1.CO.CCOC(C)=O.O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:27])([CH3:26])[C:22]([F:24])([F:23])[F:25])=[CH:17][CH:16]=2)[C@@H:11]([CH2:28][N:29]2[CH:30]3[CH2:37][CH2:36][CH2:35][CH:34]2[CH2:33][CH:32]([OH:38])[CH2:31]3)[CH2:10]1)(=[O:7])=[O:8]

Participants

7

Reactant 2

HCID 4311764Sodium borohydrideHCID 66582329HCID 66582329, compound

Product 1

HCID 66582823HCID 66582823, compoundYield 27%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of racemic 9-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-9-azabicyclo[331]nonan-3-one (81 mg, 0.142 mmol, Example 140) in 1 mL of THF and 0.3 mL of MeOH was added sodium borohydride (10.72 mg, 0.284 mmol, Sigma-Aldrich, St. Louis, Mo.). The mixture was allowed to gradually warm to room temperature and stirred for 16 h. The crude material was then diluted with EtOAc (10 mL) and water (10 mL). The organic layer was separated and the extracts were washed with water (10 mL) and brine (10 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude material was by purified via reverse-phase preparative HPLC using a Phenomenex Gemini C18 column (150×30 mm, 10 μm) eluting with 0.1% TFA in CH3CN/H2O (5% to 100% over 15 min) to give 9-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-9-azabicyclo[3.3.1]nonan-3-ol (22 mg) as a mixture of two isomers:

Workup

  1. customThe organic layer was separated
  2. washthe extracts were washed with water (10 mL) and brine (10 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customby purified via reverse-phase preparative HPLC
  7. washeluting with 0.1% TFA in CH3CN/H2O (5% to 100% over 15 min)

Sources & evidence

ORD record
ord-49e1627bf6f74354be625355d60a8d08
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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