Chloroform → 4-(4-Trifluoromethylphenyl)morpholine

HRID 1014782Notes

Reaction equation

HRID 1014782 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.CC([O-])(C)C.[Na+].C(Cl)(Cl)Cl>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2[C-](N(C)C)C=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2]>[F:9][C:8]([F:11])([F:10])[C:5]1[CH:6]=[CH:7][C:2]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:3][CH:4]=1

Participants

8

Reactant 4

HCID 6212ChloroformHCID 73941-Chloro-4-(trifluoromethyl)benzeneHCID 8083MorpholineHCID 23676156Sodium t-butoxide

Product 1

HCID 109333104-(4-Trifluoromethylphenyl)morpholineYield 77%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1317290462-Diphenylphosphino-dimethylaminoferroceneCatalystHCID 1140TolueneSolvent

Procedure

According to General Procedure B, a mixture of 4-chloro trifluoromethylbenzene (67 μL, 0.50 mmol), morpholine (52 μL, 0.60 mmol), NaOt-Bu (67 mg, 0.70 mmol), Pd2(dba)3.CHCl3 (10 mg, 0.01 mmol) and 12f (8 mg, 0.02 mmol) in PhMe (2.5 mL) was heated, cooled and filtered. Evaporation of the solvent under reduced pressure and column chromatography of the pre-adsorbed crude material (20% Et2O in hexane, silica gel) gave 52a (89 mg, 77%) as off-white crystals. 1H NMR (300 MHz, CDCl3) δ 7.50 (d, 2H, J=8.7 Hz), 6.92 (d, 2H, J=8.7 Hz), 3.87 (t, 4H, J=4.8 Hz), 3.24 (t, 4H, J=5.1 Hz); 13C NMR (75.5 MHz, CDCl3) δ 153.3, 126.4 (q, J=3 Hz), 124.6 (q, J=271 Hz), 120.9 (q, J=33 Hz) 114.3, 66.6, 48.1.

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. customEvaporation of the solvent under reduced pressure and column chromatography of the pre-adsorbed crude material (20% Et2O in hexane, silica gel)

Sources & evidence

ORD record
ord-558d9e469e8245068137d755f0a8d25f
Source dataset
uspto-grants-2011_07
Patent number
US07982064B2

Reaction notes

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