Hydrochloric Acid → Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

HRID 1883163Notes

Reaction equation

HRID 1883163 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].O.C(OCC)(=O)C.Cl>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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8857Ethyl AcetateHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

Product 1

HCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateYield 104.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 5 g of N-BOC-isonipecotic acid (21.8 mmol, Bachem) dissolved in 100 ml THF, cooled in a dry ice/acetone bath, was slowly added 43.6 ml 1 M borane-THF complex in THF (43.6 mmol). The reaction was stirred to −40 C and then replaced with an ice/water bath. After 3 hours the reaction was neutralized by careful addition of water and then worked up by addition of ethyl acetate and 1 M HCl. The layers were separated and the aqueous layer was extracted one more time with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over sodium sulfate and evaporated to give 4.9 g 4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (MS: M+H=238).

Workup

  1. temperaturecooled in a dry ice/acetone bath
  2. customreplaced with an ice/water bath
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted one more time with ethyl acetate
  5. washThe combined ethyl acetate layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-dabff5b9ab2b4348b00fef8192e9465a
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

Loading…