Sodium borohydride → 1-Cyclopropylpiperidin-4-ol

HRID 2354191Notes

Reaction equation

HRID 2354191 reaction equation
[BH4-].[Na+].[CH:3]1([N:6]2[CH2:11][CH2:10][C:9](=[O:12])[CH2:8][CH2:7]2)[CH2:5][CH2:4]1>C(O)C>[CH:3]1([N:6]2[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]2)[CH2:5][CH2:4]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 162276291-Cyclopropylpiperidin-4-one

Product 1

HCID 515828091-Cyclopropylpiperidin-4-olYield 94.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

N-benzyl-N-methyl-4-oxopiperidiumbromide (3.68 g) in water (6 ml) was added portionwise over 30 minutes to a stirred mixture of N-cyclopropylamine (0.404 g) and potassium carbonate in ethanol (15 ml) at 75° C. The mixture was stirred at 75° C. for 45 minutes. The reaction mixture was evaporated, took up into water (20 ml) and extracted into methylene chloride. The organic extracts were combined and concentrated under reduced pressure and the residue was triturated with ether and the soluble fraction was isolated by evaporation (1.11 g) to give N-cyclopropyl-4-piperidone; NMR Spectrum: (CDCl3) 0.50 (m, 4H), 1.73 (m, 1H), 2.40 (t, 4H), 2.91 (t, 4H). B) Sodium borohydride (0.085 g) was added to a stirred solution of N-cyclopropyl-4-piperidone (0.312 g) in ethanol under an atmosphere of argon. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was evaporated, took up into water (20 ml) and extracted into methylene chloride. The organic extracts were combined and concentrated under reduced pressure to give N-cyclopropyl-4-piperidinol (0.298 g); NMR Spectrum: (CDCl3) 0.50 (m, 4H), 1.35 (s, 1H), 1.55 (m, 2H), 1.86 (m, 2H) 2.34 (m, 2H), 2.89 (m, 2H), 3.70 (m, 1H). C) Using an analogous procedure to that described paragraph (A) in the portion of Example 15 which is concerned with the preparation of starting material, N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-fluoro-2-nitrobenzamide was reacted with N-cyclopropyl-4-piperidol to give N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-[(1-cyclopropylpiperidine-4-yl)oxy]-2-nitrobenzamide; Mass Spectrum: M+H+ 479.

Workup

  1. customThe reaction mixture was evaporated
  2. extractionextracted into methylene chloride
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-67855c25617f4f61a186d17d543cc9f1
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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