Triethylamine → HCID 86641444, compound

HRID 716757Notes

Reaction equation

HRID 716757 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]([CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])[CH:5]=[CH:6][CH:7]=1.[CH2:22]([NH:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH:23]=[CH2:24].CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.C(N(CC)CC)C>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[CH:16]1([CH2:15][N:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2](/[CH:24]=[CH:23]/[CH2:22][NH:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH:3]=2)[C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 558569N-Allyl-2,2,2-trifluoroacetamideHCID 86641443HCID 86641443, compound

Product 1

HCID 86641444HCID 86641444, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

N-(3-Bromophenyl)-N-(cyclohexylmethyl)-2,2,2-trifluoroacetamide (1.0 g, 2.74 mmol), N-allyl-2,2,2-trifluoroacetamide (0.5 g, 3.29 mmol), tri-O-tolylphosphine (0.08 g, 0.27 mmol) and triethylamine (2 mL, 13.7 mmol) was added to DMF and the mixture was flushed with argon for 15 min. Pd(OAc)2 (0.06 g, 0.27 mmol) was charged to the reaction mixture which was stirred at 90° C. for 2 h. The reaction mixture was cooled and partitioned between ethyl acetate and water. Organic layer was washed thoroughly with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (100-200 silica mesh, 5% to 10% EtOAc in hexane) gave (E)-N-(cyclohexylmethyl)-2,2,2-trifluoro-N-(3-(3-(2,2,2-trifluoroacetamido)prop-1-enyl)phenyl)acetamide 5 as a colorless semi solid. Yield (0.4 g, 33%); 1H NMR (400 MHz, CDCl3) δ 7.43-7.41 (m, 2H), 7.18 (s, 1H), 7.13 (d, J=6.8 Hz, 1H), 6.61 (d, J=16.0 Hz, 1H), 6.48 (bs, 1H), 6.24-6.16 (m, 1H), 4.17 (t, J=6.0 Hz, 2H), 3.62 (bs, 2H), 1.73-1.65 (m, 5H), 1.56-1.48 (m, 1H), 1.21-1.14 (m, 3H), 1.07-0.99 (m, 2H).

Workup

  1. customthe mixture was flushed with argon for 15 min
  2. temperatureThe reaction mixture was cooled
  3. custompartitioned between ethyl acetate and water
  4. washOrganic layer was washed thoroughly with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (100-200 silica mesh, 5% to 10% EtOAc in hexane)

Sources & evidence

ORD record
ord-882e50b6daa8415c88bcd8f971fd2b96
Source dataset
uspto-grants-2015_11
Patent number
US09193669B2

Reaction notes

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