Sodium cyanoborohydride → 2-[1-(3-Ethoxy-4-methyl-benzyl)-piperidin-4-yl]-2,3-dihydro-isoindol-1-one

HRID 1715157Notes

Reaction equation

HRID 1715157 reaction equation
FC(F)(F)C(O)=O.[NH:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:23])[CH2:10][CH2:9]1.[CH2:24]([O:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[CH3:35])[CH:30]=O)[CH3:25].C([BH3-])#N.[Na+]>C(O)(C)C.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[CH2:24]([O:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[CH3:35])[CH2:30][N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:23])[CH2:10][CH2:9]1)[CH3:25]

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 252420583-Ethoxy-4-methylbenzaldehydeHCID 685059012-Piperidin-4-yl-2,3-dihydro-isoindol-1-one trifluoroacetate

Product 1

HCID 685064942-[1-(3-Ethoxy-4-methyl-benzyl)-piperidin-4-yl]-2,3-dihydro-isoindol-1-oneYield 29.5%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 3776IsopropanolSolvent

Procedure

To a solution of 2-piperidin-4-yl-2,3-dihydro-isoindol-1-one trifluoroacetate (164.0 mg, 0.27 mmol, 1.0 equiv; 36% purity according to mass balance in preceeding step) in isopropanol (3.4 mL) was added 3-ethoxy-4-methyl-benzaldehyde (44.8 mg, 0.27 mmol, 1.0 equiv; intermediate B19), titanium tetra-isopropoxide (232.8 mg, 0.82 mmol, 3.0 equiv) and sodium cyanoborohydride (34.3 mg, 0.55 mmol, 2.0 equiv). The reaction mixture was allowed to react overnight and then poured directly onto a silica column. Eluting with ethyl acetate/triethylamine (98:2) yielded 29.0 mg (29%) of the title compound as white crystals. MS (ISP): 365.1 [M+H]+.

Workup

  1. customto react overnight
  2. additionpoured directly onto a silica column
  3. washEluting with ethyl acetate/triethylamine (98:2)

Sources & evidence

ORD record
ord-2234a1956eae4fd2a56d8b1d5f866d85
Source dataset
uspto-grants-2010_09
Patent number
US07799806B2

Reaction notes

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