Triethylamine → HCID 23581956, compound

HRID 238781Notes

Reaction equation

HRID 238781 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]([NH:27][C:28](=[O:39])[C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=2)([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[OH:40].[CH3:41][N:42]=[C:43]=[O:44].CCN(CC)CC>C(Cl)Cl.CCOC(C)=O>[CH3:41][NH:42][C:43](=[O:44])[O:40][C:3]1[CH:4]=[C:5]([C@:8]([C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[C:18]([F:26])[CH:17]=2)([NH:27][C:28](=[O:39])[C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:36])([F:37])[F:38])[CH:30]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:6]=[CH:7][C:2]=1[F:1]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 12228Methyl IsocyanateHCID 59458416HCID 59458416, compound

Product 1

HCID 23581956HCID 23581956, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (R)—N-(1-(4-fluoro-3-hydroxyphenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide, prepared as described in Example 264, (15 mg, 0.027 mmol), methylisocyanate (0.01 mL), and Et3N (0.02 mL) in CH2Cl2 (0.3 mL) was heated at 80° C. under microwave irradiation for 10 min. After cooling, the reaction mixture was diluted with EtOAc and the organic layer was washed with H2O, sat. NaCl, dried over Na2SO4, filtered and concentrated. The residue was purified by ISCO flash chromatography (silica gel, hexanes/EtOAc) to yield (R)-2-fluoro-5-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenyl-1-(3-(trifluoromethyl)-benzamido)-ethyl)phenyl methylcarbamate (Example 272, 11 mg, yield: 61%). LCMS: RT=2.13 min [M+H] 623.3 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm).

Workup

  1. temperatureAfter cooling
  2. washthe organic layer was washed with H2O, sat. NaCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by ISCO flash chromatography (silica gel, hexanes/EtOAc)

Sources & evidence

ORD record
ord-5b74a1bd14424665b008c1fe1eb76bd0
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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