Acetic Acid → 4-{4-[5-(4-Chlorophenyl)pyridin-2-ylethynyl]phenyl}-1-cyclopropylmethylpiperidin-4-ol

HRID 734878Notes

Reaction equation

HRID 734878 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]#[C:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4([OH:28])[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)=[CH:18][CH:17]=3)=[N:12][CH:13]=2)=[CH:4][CH:3]=1.[CH:29]1([CH:32]=O)[CH2:31][CH2:30]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C1COCC1.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]#[C:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4([OH:28])[CH2:27][CH2:26][N:25]([CH2:32][CH:29]5[CH2:31][CH2:30]5)[CH2:24][CH2:23]4)=[CH:18][CH:17]=3)=[N:12][CH:13]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 69058833HCID 69058833, compound

Product 1

HCID 578453204-{4-[5-(4-Chlorophenyl)pyridin-2-ylethynyl]phenyl}-1-cyclopropylmethylpiperidin-4-ol

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.78 g (2.02 mmol) of 4-{4-[5-(4-chlorophenyl)pyridin-2-ylethynyl]phenyl}piperidin-4-ol and 0.59 mL (8.06 mmol) of cyclopropanecarbaldehyde in 40 mL of THF was stirred for 30 minutes at RT, then combined with 1.71 g (8.06 mmol) of sodium triacetoxyborohydride and 0.46 mL (8.06 mmol) of glacial acetic acid and stirred for a further 2 days at RT. The reaction mixture was combined with DCM, and the organic phase was washed with semisaturated aqueous sodium bicarbonate solution, dried over sodium sulfate, and evaporated down in vacuo. The crude product was stirred with isopropanol, and the precipitate was filtered off and dried in vacuo. Yield: 0.19 g (21% of theoretical); C28H27ClN2O (M=442.980); calc.: molpeak (M+H)+:443/445 (Cl); found: molpeak (M+H)+:443/445 (Cl); HPLC-MS: 7.26 minutes (method A).

Workup

  1. washthe organic phase was washed with semisaturated aqueous sodium bicarbonate solution
  2. dry with materialdried over sodium sulfate
  3. customevaporated down in vacuo
  4. stirringThe crude product was stirred with isopropanol
  5. filtrationthe precipitate was filtered off
  6. customdried in vacuo
  7. custom7.26 minutes (method A)

Sources & evidence

ORD record
ord-f28eec03dd6648809f6b4096f1d8cbef
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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