Hydrochloric Acid → (3,4-Dimethyl-phenyl)-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amine

HRID 1094337Notes

Reaction equation

HRID 1094337 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10](O)=O)=[CH:5][CH:4]=1.[CH3:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=1[CH3:23])[NH2:19].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.B.O1CCCC1.Cl>ClCCl.C(OCC)(=O)C>[CH3:15][C:16]1[CH:17]=[C:18]([NH:19][CH2:10][CH2:9][C:6]2[CH:7]=[N:8][C:3]([C:2]([F:14])([F:13])[F:1])=[CH:4][CH:5]=2)[CH:20]=[CH:21][C:22]=1[CH3:23]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 72483,4-DimethylanilineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2723981Borane;tetrahydrofuran2×HCID 516957092-(6-(Trifluoromethyl)pyridin-3-yl)acetic acid

Product 1

HCID 58007591(3,4-Dimethyl-phenyl)-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amineYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (6-trifluoromethyl-pyridin-3-yl)-acetic acid (257 mg, 1.25 mmol), 3,4-dimethylaniline (167 mg, 1.38 mmol) and 1-hydroxybenzotriazole in dichloromethane (2 mL) was added under a nitrogen atmosphere 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (264 mg, 1.37 mmol) and N,N-diisopropyl ethyl amine (322 μl, 1.88 mmol). After stirring for 3 h at ambient temperature, the reaction mixture was concentrated and a solution of borane-tetrahydrofuran complex (1 M in THF, 5 mL, 5 mmol) was added and the reaction mixture was stirred for 18 h at 60° C. A further portion of the borane-tetrahydrofuran complex (1 M in THF, 5 mL, 5 mmol) was added and the reaction mixture was stirred for 4 h at 80° C. An aqueous solution of hydrochloric acid (1 M, 2 mL) was carefully added and stirring was continued for 15 min. at reflux. After cooling it was diluted with ethyl acetate (15 mL) and washed with aqueous Na2CO3 (saturated, 15 mL). The aqueous layer was extracted with EtOAc (15 mL) and the combined organic layers dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40) afforded the title compound (218 mg, 64%) as a light yellow oil. MS m/e: 295.2 [M+H]+.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. stirringthe reaction mixture was stirred for 18 h at 60° C
  3. stirringthe reaction mixture was stirred for 4 h at 80° C
  4. stirringstirring
  5. waitwas continued for 15 min.
  6. temperatureat reflux
  7. temperatureAfter cooling it
  8. washwashed with aqueous Na2CO3 (saturated, 15 mL)
  9. extractionThe aqueous layer was extracted with EtOAc (15 mL)
  10. dry with materialthe combined organic layers dried over sodium sulfate
  11. concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40)

Sources & evidence

ORD record
ord-240381d52eb24db394525f9503aeeed5
Source dataset
uspto-grants-2012_03
Patent number
US08133909B2

Reaction notes

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