1-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid → Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

HRID 1635953Notes

Reaction equation

HRID 1635953 reaction equation
[C:1]([N:8]1[CH2:16][CH2:15][CH:11]([C:12](O)=[O:13])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]>C1COCC1>[C:4]([O:3][C:1]([N:8]1[CH2:16][CH2:15][CH:11]([CH2:12][OH:13])[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

3

Reactant 1

HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

Product 1

HCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 25.03 g (109.2 mmole) N-Boc isonipecotic acid was dissolved in 200 mL TBF and treated with 200 mL 1 M borane-tetrahydrofuran complex in THF, and the mixture was stirred overnight. The mixture was concentrated under vacuum, diluted with 750 mL ethyl acetate, and washed with 150 mL 1 N HCl (6×) and then saturated brine. The organic layer was dried over sodium sulfate and concentrated to give crude product as a white solid. 1H NMR (500 MHz) δ4.15 (br d, J=13.7 Hz, 2H), 3.52 (d, J=6.2 Hz, 2H), 2.69˜2.75 (m, 2H), 1.71˜1.75 (m, 2H), 1.62˜1.70 (m, 1H), 1.47 (s, 9H), 1.12˜1.21 (m, 2H). This was used as is in the next step.

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. additiondiluted with 750 mL ethyl acetate
  3. washwashed with 150 mL 1 N HCl (6×)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customto give crude product as a white solid

Sources & evidence

ORD record
ord-136f04c392ea498899fbd6a864ac4e77
Source dataset
uspto-grants-2003_01
Patent number
US06511994B2

Reaction notes

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