Acetone → HCID 86635891, compound

HRID 914086Notes

Reaction equation

HRID 914086 reaction equation
[CH:1]1([NH:7][CH2:8][C:9]([F:16])([F:15])[C:10]([O:12]CC)=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:17]([O-:20])([O-])=[O:18].[K+].[K+].[Cl:23][C:24]1[N:29]=[C:28](Cl)[C:27]([N+:31]([O-:33])=[O:32])=[CH:26][N:25]=1.[CH3:34][C:35](C)=O>>[Cl:23][C:24]1[N:29]=[C:28]([N:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:8][C:9]([F:15])([F:16])[C:10](=[O:12])[C:17]([O:20][CH2:34][CH3:35])=[O:18])[C:27]([N+:31]([O-:33])=[O:32])=[CH:26][N:25]=1

Participants

5

Reactant 4

HCID 180Acetone2×HCID 11430Potassium CarbonateHCID 5212662,4-Dichloro-5-nitropyrimidineHCID 579555443-Cyclohexylamino-2,2-difluoropropionic acid ethyl ester

Product 1

HCID 86635891HCID 86635891, compoundYield 60%

Conditions

Temperature
0 °C

Procedure

In a round bottom flask, ethyl 3-(cyclohexylamino)-2,2-difluoropropanoate (11.05 g, 50 mmol) was dissolved in acetone (100 mL), and added K2CO3 (13.8 g, 100 mmol) to it. Cooled the round bottom flask to 0° C. in an ice bath. After 20 min, added 2,4-dichloro 5-nitropyrimidine (9.70 g, 50 mmol) in acetone (25 mL) dropwise and continued stirring for another 30 min at 0° C., then allowed to warm up to room temperature, continued for 12 hrs. Then evaporated the acetone washed with water and extracted into EtOAc (300 mL) dried over Na2SO4 and evaporated. The crude gummy solid was purified on Combiflash (ISCO) using hexane-EtOAc as solvent system to obtain the desired compound (11.85 g, 60%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.31 (m, 3H) 1.42-1.68 (m, 3H) 1.75 (d, J=9.09 Hz, 4H) 3.33 (m, 1H) 3.80 (s, 3H) 4.40 (t, J=14.02 Hz, 2H) 8.92 (s, 1H). MS (ES) [M+H] calculated for C15H19ClF2N4O4, 393. found 393.

Workup

  1. temperatureto warm up to room temperature
  2. waitcontinued for 12 hrs
  3. customThen evaporated the acetone
  4. washwashed with water
  5. extractionextracted into EtOAc (300 mL)
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe crude gummy solid was purified on Combiflash (ISCO)

Sources & evidence

ORD record
ord-924e1387a948468c89a72fa7f3188f5c
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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