2,2,2-Trifluoroethanol → HCID 57786298, compound

HRID 1628964Notes

Reaction equation

HRID 1628964 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]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([OH:26])[CH2:24][CH3:25])=[CH:4][CH:3]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[F:58][C:59]([F:63])([F:62])[CH2:60]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]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([O:26][CH2:60][C:59]([F:63])([F:62])[F:58])[CH2:24][CH3:25])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 44156374HCID 44156374, compound

Product 1

HCID 57786298HCID 57786298, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-ol (100 mg, 0.243 mmol) and 1,1′-(azodicarbonyl)dipiperdine (123 mg, 0.49 mmol) in tetrahydrofuran (5.0 mL) was added tri(n-butyl)phosphine (0.122 mL, 0.49 mmol) at room temperature. After the mixture was stirred at room temperature for 10 min under nitrogen atmosphere, 2,2,2-trifluoroethanol (0.177 mL, 2.32 mmol) was added to the reaction mixture. The mixture was stirred at 60° C. for 8 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 10-40% ethyl acetate/n-hexane gradient mixture and recrystallization from 2-propanol/n-hexane to give the title compound (41.8 mg, 0.085 mmol, 35%) as colorless crystals.

Workup

  1. stirringThe mixture was stirred at 60° C. for 8 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 10-40% ethyl acetate/n-hexane gradient mixture and recrystallization from 2-propanol/n-hexane

Sources & evidence

ORD record
ord-4ecc38bacdf242d7b5c5c4ac289bc522
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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