Methyl chloroformate → HCID 178502088, compound

HRID 896639Notes

Reaction equation

HRID 896639 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][NH:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:25]([O:27][CH3:28])=[O:26]>[OH-].[Na+].C1COCC1.CCOC(C)=O>[CH3:28][O:27][C:25](=[O:26])[N:10]([C@H:11]1[CH2:12][CH2:13][C@H:14]([C:17]2[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=2)[CH2:15][CH2:16]1)[CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 2

HCID 6586Methyl chloroformate2×HCID 178516054HCID 178516054, compound

Product 1

HCID 178502088HCID 178502088, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a stirred solution of trans-4-[4-(3-phenylpropylamino) cyclohexyl]-phenol (0.40 g, 1.3 mmol) in a mixture of 2 N NaOH (5 mL) and THF (5 mL) was added methyl chloroformate (0.12 mL, 1.6 mmol). The reaction mixture was stirred at room temperature for 2 hours. Methyl chloroformate (0.05 mL, 0.65 mmol) was added and stirring continued for another 2 hours. The mixture was diluted with EtOAc (50 mL), washed with H2O, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash chromatography (silica, 97:3 MeOH/CH2Cl2) gave trans-N-[4-(4-hydroxyphenyl)cyclohexyl]-N-(3-phenylpropyl)carbamic acid methyl ester, as an off-white solid (0.068 g, 14%): mp 128-133° C.; IR (KBr): 3403, 2923, 1673, 1518 cm−1; 1H NMR(300MHz, CD3OD) δ 7.31-7.15 (m, 5H), 7.01 (d, J=8 Hz, 2H), 6.68 (d, J=8 Hz, 2H), 3.91-3.78 (m, 1H), 3.67 (s, 3H), 3.25-3.13 (m, 2H), 2.61 (t, J=8 Hz, 2H), 2.40-2.29 (m, 1H), 1.95-1.45 (m, 10H); CI-MS (methane) (m/z): 368 [M+I]+; HRMS-API (m/z): [M+1]+ Calcd for C23H29NO3, 368.2225. found: 368.2227; HPLC: method A, 13.78 minutes (85.2%).

Workup

  1. stirringstirring
  2. waitcontinued for another 2 hours
  3. washwashed with H2O
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash chromatography (silica, 97:3 MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-7d630ba6a1e04880863a12967b627c4b
Source dataset
uspto-grants-2005_07
Patent number
US06919377B2

Reaction notes

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