Triethylamine → (R)-3-N-Boc-Amino-1-Cbz-piperidine

HRID 875614Notes

Reaction equation

HRID 875614 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.C(N(CC)CC)C.[C:22](Cl)(=[O:31])[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(Cl)Cl>[C:10]([O:9][C:8]([NH:7][C@@H:3]1[CH2:4][CH2:5][CH2:6][N:1]([C:22]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:31])[CH2:2]1)=[O:14])([CH3:11])([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protected

Product 1

HCID 50999064(R)-3-N-Boc-Amino-1-Cbz-piperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of (R)-tert-butyl piperidin-3-ylcarbamate (10.00 g, 49.93 mmol) and triethylamine (20.88 mL, 149.8 mmol) in CH2Cl2 (100 mL) at 0° C. (ice bath) was treated dropwise with benzyl carbonochloridate (10.54 mL, 74.90 mmol) and stirred at 0° C. After 2 hours, the mixture was diluted with CH2Cl2 (50 mL) and successively washed with ice cold 10% HCl (2×30 mL), water (1×30 mL), saturated NaHCO3 (1×30 mL), and brine (1×30 mL). The organic phase was dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was purified by flash chromatography on silica gel (Biotage Flash 60) eluting with 20% EtOAc/hexane (3 L). The fractions containing the product were pooled, concentrated in vacuo and dried under high vacuum for 18 hours to provide (R)-benzyl 3-(tert-butoxycarbonylamino)piperidine-1-carboxylate as a solid. LCMS (APCI+) m/z 335 (M+H)+.

Workup

  1. washsuccessively washed with ice cold 10% HCl (2×30 mL), water (1×30 mL), saturated NaHCO3 (1×30 mL), and brine (1×30 mL)
  2. dry with materialThe organic phase was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue obtained
  6. customwas purified by flash chromatography on silica gel (Biotage Flash 60)
  7. washeluting with 20% EtOAc/hexane (3 L)
  8. additionThe fractions containing the product
  9. concentrationconcentrated in vacuo
  10. customdried under high vacuum for 18 hours

Sources & evidence

ORD record
ord-1aa5126e31f34a8e9550fe96f7d1d7f8
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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