Trifluoroacetic acid → HCID 68868585, compound

HRID 1783380Notes

Reaction equation

HRID 1783380 reaction equation
[CH2:1]([C:8]1[C:9](N(C2CC2)C)=[N:10][C:11]2[C:16]([N:17]=1)=[CH:15][CH:14]=[C:13]([Cl:18])[CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C1[C:32](C#N)=[N:33][C:34]2[C:39](N=1)=[CH:38]C=C(Cl)C=2)C1C=CC=CC=1.C1([Mg]Br)CC1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([C:8]1[C:9]([CH2:32][NH:33][CH:34]2[CH2:39][CH2:38]2)=[N:10][C:11]2[C:16]([N:17]=1)=[CH:15][CH:14]=[C:13]([Cl:18])[CH:12]=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 57590375HCID 57590375, compoundHCID 68868740HCID 68868740, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 68868585HCID 68868585, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-60 °C

Procedure

(±)-(3-Benzyl-7-chloroquinoxalin-2-yl)-cyclopropyl-methylamine (16): To a stirred solution of 3-benzyl-7-chloro-2-cyanoquinoxaline (4.0 g, 14.3 mmol) in anhydrous CH2Cl2 (80 mL) at −64° C. under nitrogen was added dropwise cyclopropylmagnesium bromide (0.76 M in THF, 52 mL, 39.5 mmol). The reaction mixture was stirred at −68˜−30° C. for 40 min. It was cooled to −60° C. and TFA (12 mL) was added to the reaction mixture followed by NaBCNH3 (1.25 g, 18.9 mmol). The mixture was slowly warmed to −20° C. over 20 min, and then cooled to −30° C. and quenched with aq. NaHCO3 and extracted with CH2Cl2 (2×100 mL). The organic solution was washed with brine (60 mL), dried over MgSO4 and concentrated. Purification by flash column (SiO2, EtOAc/hexane MeOH/NH4OH 30:70:3:0.3) gave C-(3-Benzyl-7-chloro-quinoxalin-2-yl)-cyclopropyl-methylamine (16) as an oil (1.8 g). This oily product was slightly contaminated by impurities, but it was used directly for the next step without any further purification. 1H NMR (CDCl3) δ 8.02 (m, 1H), 7.96 (m, 1H), 7.67 (m, 1H), 7.19 (m, 5H), 4.52 (m, 1H), 4.41 (m, 2H), 1.37(m, 1H), 0.61 (m, 1H), 0.36 (m, 1H), 0.12 (m, 1H), 0.01 (m, 1H); MS (ESI), (M+H)+323.26, 325.26.

Workup

  1. temperatureThe mixture was slowly warmed to −20° C. over 20 min
  2. temperaturecooled to −30° C.
  3. customquenched with aq. NaHCO3
  4. extractionextracted with CH2Cl2 (2×100 mL)
  5. washThe organic solution was washed with brine (60 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customPurification by flash column (SiO2, EtOAc/hexane MeOH/NH4OH 30:70:3:0.3)

Sources & evidence

ORD record
ord-dd29ce28e6c140db85e5cc95b038e023
Source dataset
uspto-grants-2009_03
Patent number
US07501416B2

Reaction notes

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