4-Nitrophenyl chloroformate → (+)-5-Methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro 2-oxo-6-(3,4-difluorophenyl)-1-[(4-nitrophenyloxy)carbonyl]pyrimidine

HRID 650564Notes

Reaction equation

HRID 650564 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)[NH:9][C:8](=[O:19])[NH:7][C:6]=1[CH2:20][O:21][CH3:22])=[O:4].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].Cl[C:34]([O:36][C:37]1[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[CH:39][CH:38]=1)=[O:35]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)[N:9]([C:34]([O:36][C:37]2[CH:38]=[CH:39][C:40]([N+:43]([O-:45])=[O:44])=[CH:41][CH:42]=2)=[O:35])[C:8](=[O:19])[NH:7][C:6]=1[CH2:20][O:21][CH3:22])=[O:4]

Participants

5

Reactant 3

HCID 821294-Nitrophenyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 108050354-(3,4-Difluoro-phenyl)-6-methoxymethyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester

Product 1

HCID 10672264(+)-5-Methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro 2-oxo-6-(3,4-difluorophenyl)-1-[(4-nitrophenyloxy)carbonyl]pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of (+)-5-methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro-2-oxo-6-(3,4-difluorophenyl)-pyrimidine (1.98 g, 6.34 mmol) in anhydrous THF (20 mL) at −78° C. under argon atmosphere, a solution of lithium hexamethyldisilazide in THF (1M, 18 mL, 18 mmol) was added over 2-3 min. and the mixture was stirred for 10 min. This solution was added over 6 min. via a cannula to a stirred solution of 4-nitrophenyl chloroformate (4.47 g, 22.2 mmol) in THF (20 mL) at −78° C. The stirring was continued for 10 min and the mixture was poured onto ice (50 g) and extracted with chloroform (2×50 mL). The combined extracts were dried (sodium sulfate) and the solvent evaporated. The residue was purified by flash column chromatography using hexanes/ethyl acetate (4:1 to 3.5:1) as eluent. The product was obtained as a yellow syrup which on trituration with hexane became white powder (2.4 g, 79%). 1H NMR (CDC13) δ 3.522 (s, 3H), 3.744 (s, 3H), 4.65-4.80 (q, J=16.5 Hz, 2H), 6.323 (s, 1H), 7.10-7.30 (m, 4H), 7.358 (d, J=9 Hz, 2H), 8.273 (d, J=9 Hz, 2H).

Workup

  1. waitThe stirring was continued for 10 min
  2. additionthe mixture was poured onto ice (50 g)
  3. extractionextracted with chloroform (2×50 mL)
  4. dry with materialThe combined extracts were dried (sodium sulfate)
  5. customthe solvent evaporated
  6. customThe residue was purified by flash column chromatography
  7. customThe product was obtained as a yellow syrup which on trituration with hexane

Sources & evidence

ORD record
ord-2aa67c70b0484f2482fe757abc378b73
Source dataset
uspto-grants-2001_08
Patent number
US06274585B1

Reaction notes

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