Phosgene → HCID 58968698, compound

HRID 2075064Notes

Reaction equation

HRID 2075064 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:40]([CH:43](C)C)CC)(C)C.C(Cl)(Cl)=[O:47].[OH-].[NH4+]>ClCCl>[F:24][C:23]([F:26])([F:25])[C:15]1[CH:14]=[C:13]([CH:18]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:16]=1)[CH2:12][N:11]([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])[C:43]([NH2:40])=[O:47]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 14923Ammonium HydroxideHCID 81531DiisopropylethylamineHCID 58968615N-(2-(cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyl)(3,5-bis(trifluoromethyl)phenyl)methanamine

Product 1

HCID 58968698HCID 58968698, compoundYield 32.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3,5-bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-amine (Example 41, STEP E, 20 mg, 0.038 mmol) in dichloromethane (1 ml) was added diisopropylethyl amine (6 mg, 0.045 mmol) followed by phosgene (18.8 mg, 0.038 mmol) at room temperature and stirred for 1 hour. Reaction mixture was then treated with concentrated ammonium hydroxide (0.5 ml) and stirred at room temperature for overnight. The reaction mixture was diluted with dichloromethane, washed with water, dried over anhydrous magnesium sulphate and concentrated in vacuo. The product was purified on Biotage column (12+S), eluting with 2% ethyl acetate in heptane (1CV), 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) 1.59 (m, 4H) 1.67 (s, 1H) 1.94 (d, J=12.4 Hz, 1H) 3.1 (s, 3H) 3.92 (d, J=7.8 Hz, 1H) 4.6 (m, 4H) 7.36 (s, 1H) 7.45 (d, J=7.9 Hz, 1H) 7.53 (d, J=8.3 Hz, 1H) 7.68 (s, 2H) 7.78 (s, 1H). MS (ES+) Calc: 570.2, Found: 615.6 (M+45).

Workup

  1. customReaction mixture
  2. stirringstirred at room temperature for overnight
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe product was purified on Biotage column (12+S)
  7. washeluting with 2% ethyl acetate in heptane (1CV), 2-20% (10CV), 20% (2CV)

Sources & evidence

ORD record
ord-530dcd8b75814c8da41afa6d0a74e712
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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