2,2,2-Trifluoroethanol → HCID 57786011, compound

HRID 1399236Notes

Reaction equation

HRID 1399236 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=4[CH3:23])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([CH:26]2[CH2:28][CH2:27]2)[OH:25])=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[F:60][C:61]([F:65])([F:64])[CH2:62]O>O1CCCC1>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=4[CH3:23])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([CH:26]2[CH2:28][CH2:27]2)[O:25][CH2:62][C:61]([F:65])([F:64])[F:60])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 57786077HCID 57786077, compound

Product 1

HCID 57786011HCID 57786011, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [9-chloro-1-(4-methoxy-2-methylphenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](cyclopropyl)methanol (82 mg, 0.21 mmol) and tributyl phosphine (0.10 mL, 0.41 mmol) in tetrahydrofuran (0.84 mL) was added 1,1′-(azodicarbonyl) dipiperidine (104 mg, 0.41 mmol), and the mixture was stirred at room temperature for 10 min. To the reaction mixture was added 2,2,2,-trifluoroethanol (0.15 mL, 2.06 mmol), and the mixture was stirred at 60° C. for 1 h. The reaction mixture was cooled at room temperature and concentrated in vacuo. The residue was diluted with diethyl ether. The residual solid was removed by filtration. The filtrate was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 40% ethyl acetate/n-hexane mixture. The desired fractions were concentrated in vacuo. The residual oil was crystallized from ethyl acetate/diisopropyl ether to give the title compound as a colorless crystal (35.8 mg, 0.075 mmol, 36%).

Workup

  1. stirringthe mixture was stirred at 60° C. for 1 h
  2. temperatureThe reaction mixture was cooled at room temperature
  3. concentrationconcentrated in vacuo
  4. additionThe residue was diluted with diethyl ether
  5. customThe residual solid was removed by filtration
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel eluting with a 40% ethyl acetate/n-hexane mixture
  8. concentrationThe desired fractions were concentrated in vacuo
  9. customThe residual oil was crystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-a9450be21ec144f9a33ef689b901a700
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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