Diisopropylamine → Dimethyl-[3-(4-nitro-2-trifluoromethyl-phenyl)-prop-2-ynyl]-amine

HRID 1660977

Reaction equation

HRID 1660977 reaction equation
P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.[CH3:14][N:15]([CH3:19])[CH2:16][C:17]#[CH:18].N(C(C)C)C(C)C.[N+:27]([C:30]1[CH:31]=[CH:32][C:33](Br)=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)([O-:29])=[O:28]>O1CCOCC1.CCOC(C)=O.O.[Cu]I.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl>[CH3:14][N:15]([CH3:19])[CH2:16][C:17]#[C:18][C:33]1[CH:32]=[CH:31][C:30]([N+:27]([O-:29])=[O:28])=[CH:35][C:34]=1[C:36]([F:37])([F:38])[F:39]

Participants

10

Reactant 4

HCID 7912DiisopropylamineHCID 81643N,N-DimethylpropargylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 1361982-Bromo-5-nitrobenzotrifluoride

Product 1

HCID 67021317Dimethyl-[3-(4-nitro-2-trifluoromethyl-phenyl)-prop-2-ynyl]-amine

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

t-Bu3P (0.25 M in dioxane, 8.9 mL, 2.2 mmol, 0.2 equiv), 3-dimethylamino-1-propyne (FLUKA) (1.65 mL, 15.6 mmol, 1.4 equiv), and i-Pr2NH (2.0 mL, 14.4 mmol, 1.3 equiv) are added sequentially to a mixture of 5-nitro-2-bromobenzotrifluoride (ALDRICH) (3 g, 11.1 mmol), CuI (0.148 g, 0.78 mmol, 0.07 equiv), and Pd(PhCN)2Cl2 (0.427 g, 1.1 mmol, 0.1 equiv) in dioxane (10 mL). The reaction mixture is stirred for 48 h at rt. Then, Pd(PhCN)2Cl2 (0.100 g) is added. After stirring for additional 24 h, the reaction mixture is diluted with EtOAc and H2O and filtered through a pad of Celite. The filtrate is extracted with EtOAc. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude material by silica gel column chromatography (CH2Cl2/NH3 (2 N in MeOH), 95:5) affords the title compound as a brown oil: ES-MS: 273.0 [M+H]+; single peak at tR=3.06 min (System 1); Rf=0.13 (CH2Cl2/NH3 (2 N in MeOH), 95:5).

Workup

  1. stirringAfter stirring for additional 24 h
  2. filtrationfiltered through a pad of Celite
  3. extractionThe filtrate is extracted with EtOAc
  4. washThe organic phase is washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude material by silica gel column chromatography (CH2Cl2/NH3 (2 N in MeOH), 95:5)

Sources & evidence

ORD record
ord-48463f684ac441b68d3df8c38e2b99c5
Source dataset
uspto-grants-2011_10
Patent number
US08030311B2

Linked notes

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