2-Fluoroethanol → HCID 86689162, compound

HRID 1752482Notes

Reaction equation

HRID 1752482 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8](=[O:15])[NH:9][C:10]=1[NH:11][C:12](=[O:14])[CH3:13])=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[F:47][CH2:48][CH2:49]O.C([O-])(O)=O.[Na+]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12](=[O:14])[CH3:13])=[N:9][C:8]([O:15][CH2:49][CH2:48][F:47])=[CH:7][N:6]=1)=[O:4]

Participants

7

Reactant 5

HCID 97372-Fluoroethanol3×HCID 11776Triphenylphosphine3×HCID 220568ethyl N-ethoxycarbonyliminocarbamate3×HCID 516892Sodium BicarbonateHCID 71271234HCID 71271234, compound

Product 1

HCID 86689162HCID 86689162, compoundYield 205.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 3-acetylamino-5-oxo-4,5-dihydro-pyrazine-2-carboxylic acid methyl ester (300 mg, 1.136 mmol, 80% purity) in dry THF (8 ml) under argon were added triphenylphosphine (119 mg, 0.455 mmol) and diethyl azodicarboxylate (DEAD, 0.072 ml, 0.455 mmol) at −10° C. The reaction was stirred at −10° C. for 15 min and then 2-fluoro-ethanol (0.033 ml, 0.568 mmol) was added. The reaction was stirred at rt for 15 min. To complete the reaction, more triphenylphosphine (119 mg, 0.455 mmol) and DEAD (0.072 ml, 0.455 mmol) were added at −10° C. and the resulting mixture was stirred at −10° C. for 15 min before the addition of 2-fluoro-ethanol (0.033 ml, 0.568 mmol). The reaction was stirred for 100 min. More triphenylphosphine (119 mg, 0.455 mmol) and DEAD (0.072 ml, 0.455 mmol) were added at −10° C. and the resulting mixture was stirred at −10° C. for 15 min before the addition of 2-fluoroethanol (0.033 ml, 0.568 mmol). The reaction was stirred for another 2 h. Saturated aq. NaHCO3 was added and the mixture was extracted with EtOAc, the combined organic layers were washed with aq. sodium chloride, filtered and dried with Na2SO4 and evaporated. The residue was purified by chromatography on silica gel (DCM to DCM/EtOAc 9:1) to provide the title compound as yellow oil (300 mg).

Workup

  1. stirringThe reaction was stirred at rt for 15 min
  2. additionwere added at −10° C.
  3. stirringThe reaction was stirred for 100 min
  4. stirringThe reaction was stirred for another 2 h
  5. extractionthe mixture was extracted with EtOAc
  6. washthe combined organic layers were washed with aq. sodium chloride
  7. filtrationfiltered
  8. dry with materialdried with Na2SO4
  9. customevaporated
  10. customThe residue was purified by chromatography on silica gel (DCM to DCM/EtOAc 9:1)

Sources & evidence

ORD record
ord-b3c6f381b0f64fa2892241eed268140e
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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