Water → Benzyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)piperazine-1-carboxylate

HRID 1500518Notes

Reaction equation

HRID 1500518 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClC(Cl)C.C(O)(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH:27]2[CH2:28][CH2:29][N:24]([C:22]([O:21][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:23])[CH2:25][CH2:26]2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 643495Benzyl piperazine-1-carboxylateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 18971584Benzyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)piperazine-1-carboxylateYield 74%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of piperazine-1-carboxylic acid benzyl ester (6.6 g, 29.96 mmol) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester in dichloroethane (150 mL) containing two drops of acetic acid was stirred at RT for 1 h and then sodium triacetoxyborohydride (19.05 g, 89.89 mmol) was added in portions. The reaction mixture was stirred at RT overnight, water (150 mL) was added, and the reaction mixture was stirred at RT for 2 h. The reaction mixture was extracted with DCM (4×30 mL). Combined organic layers were dried over sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel chromatography (20-30% EtOAc/petroleum ether) to provide the title intermediate (9 g, 74% yield) as a colorless oil. (m/z): [M+H]+ calcd for C22H33N3O4 404.25, found 404.3.

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. stirringthe reaction mixture was stirred at RT for 2 h
  3. extractionThe reaction mixture was extracted with DCM (4×30 mL)
  4. dry with materialCombined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by silica gel chromatography (20-30% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-2678d2562eff463aab5d83ef934c8f86
Source dataset
uspto-grants-2015_12
Patent number
US09206159B2

Reaction notes

Loading…