Potassium Carbonate → Ethyl 3-[(2-chloro-5-nitropyrimidin-4-YL)(cyclopentyl)amino]-2,2-difluoropropanoate

HRID 914052Notes

Reaction equation

HRID 914052 reaction equation
[CH:1]1([NH:6][CH2:7][C:8]([F:15])([F:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[Cl:22][C:23]1[N:28]=[C:27](Cl)[C:26]([N+:30]([O-:32])=[O:31])=[CH:25][N:24]=1>CC(C)=O>[Cl:22][C:23]1[N:28]=[C:27]([N:6]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH2:7][C:8]([F:14])([F:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:26]([N+:30]([O-:32])=[O:31])=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5212662,4-Dichloro-5-nitropyrimidineHCID 57634998Ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate

Product 1

HCID 57955636Ethyl 3-[(2-chloro-5-nitropyrimidin-4-YL)(cyclopentyl)amino]-2,2-difluoropropanoateYield 53.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

Compound Ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate (396 mg, 1.79 mmol) was solubilized in acetone (40 mL, dry). The solution was cooled in an ice salt bath under a nitrogen atmosphere and K2CO3 (495 mg, 3.58 mmol) added. To this, a solution of 2,4-dichloro-5-nitropyrimidine (378 mg, 1.97 mmol) in acetone (10 mL, dry) was added dropwise. Upon completion of addition the reaction mixture abandoned and allowed to slowly warm to room temperature and stir overnight. The mixture was then filtered through paper, the filter pad washed with acetone, and the filtrate concentrated. The concentrate was then solubilized in EtOAc (10 mL). Hexanes (70 mL) were then added and the solution was put on the rotovap to slowly concentrate. Yellow crystals form and are collected by filtration to yield 360 mg of the desired product Ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(cyclopentyl)amino)-2,2-difluoropropanoate (53%). The filtrate was found to contain a 1:1:1 mixture of the product, dichloronitropyrimidine, and the 2-addition product. This material was concentrated and set aside for future use. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (t, J=7.20 Hz, 3H) 1.36-1.98 (m, 8H) 3.64 (q, 1H) 4.25 (q, J=7.24 Hz, 2H) 4.35 (t, J=13.77 Hz, 2H) 8.94 (s, 1H). [M+H] calc'd for C14H17F2N4O4, 379. found 379.

Workup

  1. temperatureThe solution was cooled in an ice salt bath under a nitrogen atmosphere
  2. additionUpon completion of addition the reaction mixture
  3. filtrationThe mixture was then filtered through paper
  4. washthe filter pad washed with acetone
  5. concentrationthe filtrate concentrated
  6. additionHexanes (70 mL) were then added
  7. concentrationto slowly concentrate
  8. filtrationYellow crystals form and are collected by filtration

Sources & evidence

ORD record
ord-f545c6771fcd496d8ad394b05d9c4cf9
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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