Toluene → HCID 57979762, compound

HRID 1868097Notes

Reaction equation

HRID 1868097 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.Br[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]([F:18])([F:17])[F:16].CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>ClCCl.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][C@H:2]1[NH:3][CH2:4][CH2:5][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([F:18])([F:17])[F:16])[CH2:7]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 73304342-Methylpiperazine, (R)-2×HCID 23676156Sodium t-butoxide

Product 1

HCID 57979762HCID 57979762, compoundYield 185.1%

Reagents, catalysts & solvents 2

HCID 634876Binap, (A+-)-CatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of (R)-2-methyl-piperazine (300 mg, 2.99 mmol), 2-bromo benzotrifluoride (612 mg, 2.72 mmol), tris(dibenzylidineacetone)dipalladium (0) (24.72 mg, 0.027 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (51.06 mg, 0.082 mmol) and sodium tert-butoxide (326.77 mg, 3.4 mmol) were charged to a microwave vial. Toluene (3.0 mL) was introduced under nitrogen atmosphere and the reaction mixture was irradiated at 110° C. for 30 minutes. Reaction was complete as determined by TLC. The reaction was repeated at (R)-2-methyl-piperazine (1.0 g, 9.98 mmol). Reaction mixtures were combined, diluted with dichloromethane, washed with water, saturated brine then dried over Na2SO4 and concentrated. The crude product was purified via flash column chromatography to yield (R)-3-methyl-1-(2-trifluoromethyl-phenyl)-piperazine as yellow oil (1.23 g, 39.6% yield). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.07 (d, J=6.32 Hz, 3H) 2.41-2.51 (m, 1H) 2.74-2.84 (m, 1H) 2.90-2.98 (m, 2H) 3.00-3.13 (m, 3H) 7.18-7.25 (m, 1H) 7.35 (d, J=8.08 Hz, 1H) 7.47-7.55 (m, 1H) 7.62 (d, J=7.83 Hz, 1H).

Workup

  1. additionwere charged to a microwave vial
  2. customthe reaction mixture was irradiated at 110° C. for 30 minutes
  3. customReaction
  4. customReaction mixtures
  5. washwashed with water, saturated brine
  6. dry with materialthen dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified via flash column chromatography

Sources & evidence

ORD record
ord-1d5c6288110640b2b06771442ccb77f9
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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