2,2,2-Trifluoroethanol → HCID 57785949, compound

HRID 1399326Notes

Reaction equation

HRID 1399326 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[Cl:23])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([OH:27])[CH2:25][CH3:26])=[CH:4][CH:3]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[F:59][C:60]([F:64])([F:63])[CH2:61]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[Cl:23])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([O:27][CH2:61][C:60]([F:64])([F:63])[F:59])[CH2:25][CH3:26])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 57785912HCID 57785912, compound

Product 1

HCID 57785949HCID 57785949, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[9-chloro-1-(2-chloro-4-methoxyphenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-ol (110 mg, 0.27 mmol), 1,1′-(azodicarbonyl)dipiperidine (137 mg, 0.54 mmol) in tetrahydrofuran (5.0 mL) was added tri(n-butyl)phosphine (0.136 mL, 0.54 mmol) at room temperature. After the mixture was stirred at room temperature for 10 min under nitrogen atmosphere, 2,2,2-trifluoroethanol (0.197 mL, 2.70 mmol) was added to the reaction mixture. The mixture was stirred at 60° C. for 6 hr under nitrogen atmosphere. The mixture was concentrated in vacuo and diethyl ether was added to the residue. The solid was removed by filtration and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 10-30% ethyl acetate/n-hexane gradient mixture and recrystallization from ethyl acetate/n-hexane to give the title compound (43.3 mg, 0.089 mmol, 33%) as colorless crystals.

Workup

  1. stirringThe mixture was stirred at 60° C. for 6 hr under nitrogen atmosphere
  2. concentrationThe mixture was concentrated in vacuo and diethyl ether
  3. additionwas added to the residue
  4. customThe solid was removed by filtration
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel eluting with a 10-30% ethyl acetate/n-hexane gradient mixture and recrystallization from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-45f2b6573c5d4ee6845d8929b662fca3
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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