Benzyl chloroformate → Benzyl 1-cyclohexyl-4-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate

HRID 2362944Notes

Reaction equation

HRID 2362944 reaction equation
Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].Cl.[CH:13]1([N:19]2[C:23]3([CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[C:22](=[O:29])[NH:21][CH2:20]2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>N1C=CC=CC=1>[CH:13]1([N:19]2[C:23]3([CH2:24][CH2:25][N:26]([C:2]([O:4][CH2:5][C:6]4[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=4)=[O:3])[CH2:27][CH2:28]3)[C:22](=[O:29])[NH:21][CH2:20]2)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

4

Reactant 2

HCID 10387Benzyl chloroformateHCID 1317312981-Cyclohexyl-1,3,8-triazaspiro[4.5]decan-4-one, hydrochloride

Product 1

HCID 58046657Benzyl 1-cyclohexyl-4-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Benzyl chloroformate (1.74 mL, 0.0116 mmol) was added dropwise at 0° C. to 1-cyclohexyl-1,3,8-triazaspiro[4.5]decan-4-one, hydrochloride (prepared as described in J. Med. Chem. 1998, 41, 5084-5093); 1H NMR (DMSO-d6); δ1.11 (m, 2H); 1.24 (m, 4H); 1.58 (m, 4H); 1.77 (m, 4H); 2.38 (m, 2H); 3.32 (m, 3H); 4.21 (s, 2H); 9.35 (br s, 1H); 12.7 (br s, 1H); (3.59 g, 0.0116 mol) in pyridine (35 mL). The mixture was allowed to warm to room temperature and then evaporated. The residue was diluted with ethyl acetate, washed with water and brine, dried (MgSO4) and evaporated. The residue was purified by Biotage flash chromatography (5% methanol/dichloromethane) to give product as a white solid (2.15 g, 50%); 1H NMR (DMSO-d6); δ1.04 (m, 1H); 1.23-1.31 (m, 4H); 1.55-1.58 (m, 6H); 1.67 (d, J=10.4 Hz, 2H); 2.52 (m, 2H); 3.51 (m, 2H); 3.74-3.77 (m, 2H); 4.10 (s, 2H); 5.08 (s, 2H); 7.31-7.39 (m, 5H); 8.20 (br s, 1H).

Workup

  1. customevaporated
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by Biotage flash chromatography (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-3ac22a412b074d72990e202c2ab99e4e
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

Loading…