Sodium Hydroxide → tert-butyl (3R)-3-(hydroxymethyl)piperidine-1-carboxylate

HRID 1435150Notes

Reaction equation

HRID 1435150 reaction equation
B.O1CCCC1.[C:7]([N:14]1[CH2:22][CH2:21][CH2:20][C@@H:16]([C:17](O)=[O:18])[CH2:15]1)([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[OH-].[Na+]>C1COCC1>[OH:18][CH2:17][C@@H:16]1[CH2:20][CH2:21][CH2:22][N:14]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:15]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 6435161-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylateHCID 2723981Borane;tetrahydrofuran

Product 1

HCID 1514447tert-butyl (3R)-3-(hydroxymethyl)piperidine-1-carboxylateYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Borane-tetrahydrofuran complex (1M in THF) (65.4 ml, 65.4 mmol, 3 eq) is added dropwise to a solution of (R)-(−)-N-Boc-nipecotic acid (5 g, 21.8 mmol, 1 eq) in THF (50 ml) and this is stirred at room temperature for 16 hours. The solution is cooled to 0° C. and carefully hydrolysed with 2N aqueous sodium hydroxide (250 ml) the resulting mixture is then heated for 48 hrs. The mixture is cooled to 0° C. and extracted with diethyl ether (3×100 ml). The organic layers are combined, washed with brine (100 ml), dried over magnesium sulphate, filtered and concentrated in vacuo. The residue is purified by flash chromatography, eluting with 50-70% ethyl acetate in iso-hexane to give the tert-butyl (3R)-3-(hydroxymethyl)piperidine-1-carboxylate (4.56 g, 98%). 1H NMR (300 MHz, CDCl3) δH: 4.0-2.7 (6H, br m), 2.17-1.19 (5H, br m) 1.46 (9H, s).

Workup

  1. temperatureis then heated for 48 hrs
  2. temperatureThe mixture is cooled to 0° C.
  3. extractionextracted with diethyl ether (3×100 ml)
  4. washwashed with brine (100 ml)
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by flash chromatography
  9. washeluting with 50-70% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-2e0acbd2c7414c3192d2e94eb2841699
Source dataset
uspto-grants-2009_11
Patent number
US07615648B2

Reaction notes

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