Diethyl Ether → HCID 86585778, compound

HRID 2122192Notes

Reaction equation

HRID 2122192 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([N:10]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)CC(O)C(F)(F)F)[CH:6]=[CH:7][C:8]=1Br.C([Sn]([C:44]#[C:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)(CCCC)CCCC)CCC.C(C1C=CC(C#C[SnH3])=C(CCCC)C=1CCCC)CCC.C([O:75][CH2:76][CH3:77])C>[F-].[K+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:46]1([C:45]#[C:44][C:8]2[CH:7]=[CH:6][C:5]([N:10]([C:76]([OH:75])([CH3:77])[C:2]([F:30])([F:29])[F:1])[CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:26])[F:28])[CH:20]=3)=[CH:4][C:3]=2[C:2]([F:30])([F:29])[F:1])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 630640Tributyl(2-phenylethynyl)stannaneHCID 23506062HCID 23506062, compoundHCID 178440888HCID 178440888, compound

Product 1

HCID 86585778HCID 86585778, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 522689Potassium FluorideSolvent

Procedure

The 3-[(3-(trifluoromethyl)-4-bromophenyl)[[3-(1,1,1-trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol (0.33 g, 0.648 mmol) and tributylstannylphenyl-acetylene (0.278 g, 0.712 mmol) were added to degassed 1,2-dichloroethane. The resulting mixture was stirred at room temperature for 10 min, then Pd(PPh3)2Cl2 (0.032 g. 0.045 mmol) was added. The mixture was stirred 18 h at room temperature. More tributyl-stannylphenylacetylene (0.278 g, 0.712 mmol) and Pd(PPh3)2Cl2 (0.032 g, 0.045 mmol) were added. The solution was refluxed for 72 h. The reaction mixture was diluted with diethyl ether and stirred in 10% aq. KF for 18 h. The organic layer was collected, dried over MgSO4 and concentrated. The crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane to give 0.102 g (30%) of the desired 3-[[+(phenylethynyl)-(3-(trifluoromethyl)phenyl]-[[3-(trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro2-propanol product as a pure yellow oil. Anal calcd. For C26H18NOF9: C, 58.76; H, 3.41; N, 2.64. Found: C, 58.72; H, 3.67; N, 2.47. HRMS calcd. 532.1322 [M+H]+, found: 532.1304. 1H NMR (CDCl3) δ 7.52 (m, 4H), 7.38 (dd, 2H), 7.32 (dd, 2H), 7.24 (dd, 1H), 7.00 (s, 1H), 6.78 (dd, 1H), 4.80 (s, 2H), 4.36 (m, 1H), 3.92 (d, 1H), 3.65 (m, 1H), 2.60 (d, 1H). 19F NMR (CDCl3) δ −63.5 (s, 6F), −79.38 (d, 3F).

Workup

  1. customto degassed 1,2-dichloroethane
  2. stirringThe mixture was stirred 18 h at room temperature
  3. temperatureThe solution was refluxed for 72 h
  4. customThe organic layer was collected
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane
  8. customto give 0.102 g (30%) of the

Sources & evidence

ORD record
ord-7530c0a9273f44439aff18310066fb1c
Source dataset
uspto-grants-2004_02
Patent number
US06696472B2

Reaction notes

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