Triethylamine → n-Cbz-3-hydroxypiperidine

HRID 1291845Notes

Reaction equation

HRID 1291845 reaction equation
[CH2:1]([O:8][C:9](Cl)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[OH:13][CH:14]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]1.C(N(CC)CC)C>ClCCl>[CH2:1]([O:8][C:9]([N:16]1[CH2:17][CH2:18][CH2:19][CH:14]([OH:13])[CH2:15]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 2723962Piperidine-3-ol hydrochloride

Product 1

HCID 561665n-Cbz-3-hydroxypiperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Benzylchloroformate (15 ml) was added dropwise to a stirred suspension of 3-hydroxypiperidine hydrochloride (13.7 g) and triethylamine (30 ml) in dichloromethane (150 ml), maintaining the temperature below 15° C. throughout. Stirring was continued for three hours, then the solution was washed with water (4×100 ml) and saturated aqueous sodium chloride (100 ml), dried (PS paper) and concentrated. The residual oil was dissolved in ether (300 ml), washed with dilute hydrochloric acid (2×100 ml) and water (100 ml), dried (PS paper) and concentrated. The residue was purified by flash column chromatography, eluting first with hexane/ether (1:1) then ether to give 1-benzyloxycarbonylpiperidine-3-ol (7.1 g) as a colourless oil. NMR(d6DMSO): δ 1.2-1.4(2H,m); 1.6-1.9(1H,m+1H,m); 2.8(1H,br s); 2.95(1H,m); 3.45(1H,m); 3.65(1H,br.d); 3.8(1H,dd); 4.85(1H,d); 5.1(2H,s); 7.3(5H,m); m/e 236(M+H)+.

Workup

  1. temperaturemaintaining the temperature below 15° C. throughout
  2. washthe solution was washed with water (4×100 ml) and saturated aqueous sodium chloride (100 ml)
  3. customdried (PS paper)
  4. concentrationconcentrated
  5. dissolutionThe residual oil was dissolved in ether (300 ml)
  6. washwashed with dilute hydrochloric acid (2×100 ml) and water (100 ml)
  7. customdried (PS paper)
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography
  10. washeluting first with hexane/ether (1:1)

Sources & evidence

ORD record
ord-0587f44b689a4b4191d9953dd2e4aff2
Source dataset
uspto-grants-1998_05
Patent number
US05753659

Reaction notes

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