Acetic Acid → HCID 86714787, compound

HRID 2171935Notes

Reaction equation

HRID 2171935 reaction equation
O=[C:2]([C:9]1([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12][CH2:11][CH2:10]1)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].C([O-])(=O)C.[NH4+].C(O)(=O)C.[C:27]([BH3-])#[N:28].[Na+].[Cl:31][C:32]1[N:37]=C(Cl)[C:35]([F:39])=[CH:34][N:33]=1.C(N(CC)C(C)C)(C)C>CCO>[Cl:31][C:32]1[N:37]=[C:27]([NH:28][CH:2]([C:9]2([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:35]([F:39])=[CH:34][N:33]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 71247740HCID 71247740, compound2×

Product 1

HCID 86714787HCID 86714787, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 3-oxo-3-(1-(trifluoromethyl)cyclopentyl)propanoate, 195a, (0.500 g, 1.982 mmol) and ammonium acetate (0.458 g, 5.946 mmol) in EtOH (20 mL) was warmed to reflux for 3 hours. The crude reaction was concentrated in vacuo to a residue and redissolved in EtOAc (20 mL). The new mixture was cooled to 0° C., and acetic acid (0.338 mL, 5.946 mmol) and sodium cyanoborohydride (0.498 g, 7.928 mmol, 4 equiv) were added to the mixture. The reaction was allowed to warm to room temperature and stirred overnight. The reaction was quenched with aqueous saturated sodium bicarbonate solution (10 mL) and extracted with ethyl acetate (2×20 mL). The organic phase was concentrated in vacuo and redissolved in EtOH (20 mL). To the solution was added 2,4-dichloro-5-fluoro-pyrimidine (0.496 g, 2.973 mmol) and N,N-diisopropylethylamine base (2.0 mL). The reaction was refluxed for 12 hours and then concentrated in vacuo. The residue was purified by silica gel chromatography (EtOAc) yielding 84 mg of the desired product as a yellow oil: LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.54 minutes (M+H) 384.40.

Workup

  1. temperatureto reflux for 3 hours
  2. customThe crude reaction
  3. concentrationwas concentrated in vacuo to a residue
  4. dissolutionredissolved in EtOAc (20 mL)
  5. temperatureto warm to room temperature
  6. customThe reaction was quenched with aqueous saturated sodium bicarbonate solution (10 mL)
  7. extractionextracted with ethyl acetate (2×20 mL)
  8. concentrationThe organic phase was concentrated in vacuo
  9. dissolutionredissolved in EtOH (20 mL)
  10. temperatureThe reaction was refluxed for 12 hours
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by silica gel chromatography (EtOAc)

Sources & evidence

ORD record
ord-08d976dae80b4ecea0c2a8f4b6323c2e
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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