Methyl chloroformate → (3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-carbamic acid methyl ester

HRID 2075062Notes

Reaction equation

HRID 2075062 reaction equation
[CH:1]1([CH:7]([O:35][CH3:36])[C:8]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:9]=2[CH2:10][NH:11][CH2:12][C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([C:23]([F:26])([F:25])[F:24])[CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.Cl[C:47]([O:49][CH3:50])=[O:48]>ClCCl>[CH3:50][O:49][C:47](=[O:48])[N:11]([CH2:12][C:13]1[CH:14]=[C:15]([C:23]([F:26])([F:25])[F:24])[CH:16]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:18]=1)[CH2:10][C:9]1[CH:27]=[C:28]([C:31]([F:32])([F:33])[F:34])[CH:29]=[CH:30][C:8]=1[CH:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[O:35][CH3:36]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 58968615N-(2-(cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyl)(3,5-bis(trifluoromethyl)phenyl)methanamine

Product 1

HCID 58968645(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-carbamic acid methyl esterYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3,5-bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-amine (Example 41, STEP E, 22 mg, 0.042 mmol) in dichloromethane (1 ml) was added diisopropylethyl amine (8.09 mg, 0.063 mmol) followed by methyl chloroformate (3.94 mg, 0.042 mmol) at room temperature and stirred for overnight. Reaction mixture was then concentrated in vacuo and the product was purified on Biotage column (12+S), eluting with 2% ethyl acetate in heptane (1 CV), 2-20% (10CV), 20% (2CV) to yield the title compound (7 mg, 30%) as colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.0 (m, 6H) 1.4(m, 1H) 1.5(m, 2H) 1.7(s, 1H) 1.9 (d, J=11.2 Hz, 1H) 3.0 (s, 3H) 3.8(s, 3H) 4.0 (d, J=17.9 Hz, 1H) 4.6 (m, 4H) 7.25 (d, J=10.4 Hz, 1H) 7.45 (d, J=7.5 Hz, 1H) 7.53 (m, 3H) 7.7 (s, 1H) 7.8 (s, 1H). MS (ES+) Calc: 585.2, Found: 630.3 (M+45).

Workup

  1. customReaction mixture
  2. concentrationwas then concentrated in vacuo
  3. customthe product was purified on Biotage column (12+S)
  4. washeluting with 2% ethyl acetate in heptane (1 CV), 2-20% (10CV), 20% (2CV)

Sources & evidence

ORD record
ord-ef1f41a5f86846df9b9e1d62def13e55
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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