Phosphorus oxychloride → HCID 178457491, compound

HRID 2169202Notes

Reaction equation

HRID 2169202 reaction equation
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:24])[NH:11][C:10]=1[C:25]([OH:27])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:28]([O:35][CH2:36][CH2:37][NH:38][CH:39]([CH3:41])[CH3:40])([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[Si:28]([O:35][CH2:36][CH2:37][N:38]([CH:39]([CH3:41])[CH3:40])[C:25]([C:10]1[NH:11][C:12]([CH2:16][C:17]2[C:18]([Cl:24])=[CH:19][CH:20]=[CH:21][C:22]=2[Cl:23])=[N:13][C:14](=[O:15])[C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:27])([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 57917054N-(2-((tert-butyldimethylsilyl)oxy)ethyl)propan-2-amineHCID 178524913HCID 178524913, compound

Product 1

HCID 178457491HCID 178457491, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

5-(Benzyloxy)-2-(2,6-dichlorobenzyl)-6-oxo-3,6-dihydro-pyrimidine-4-carboxylic acid (62) (0.2 g, 494 μmol, Eq: 1.00) and N-(2-(tert-butyldimethylsilyloxy)ethyl)propan-2-amine (118 mg, 543 μmol, Eq: 1.1) were dissolved in pyridine (3 ml) and cooled in an ice/NaCl bath. POCl3 (227 mg, 138 μl, 1.48 mmol, Eq: 3) was added dropwise. After the addition was complete, stirring of the reaction mixture was continued at 0° C. for approx. 40 minutes. The reaction mixture was quenched with ice and extracted twice with ethyl acetate. The organic layers were washed with NaHCO3, were combined, dried over Na2SO4, filtered and concentrated. The remaining oil was purified by SiO2 flash chromatography (24 g SiO2, hexanes/ethyl acetate 0-50% ethyl acetate). Product containing fractions were combined and concentrated. The remaining oil was treated with hexanes and concentrated again to afford 5-benzyloxy-2-(2,6-dichlorobenzyl)-6-oxo-3,6-dihydro-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (63) (0.17 g, 281 μmol, 57.0% yield) as a white solid.

Workup

  1. temperaturecooled in an ice/NaCl bath
  2. additionAfter the addition
  3. customThe reaction mixture was quenched with ice
  4. extractionextracted twice with ethyl acetate
  5. washThe organic layers were washed with NaHCO3
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe remaining oil was purified by SiO2 flash chromatography (24 g SiO2, hexanes/ethyl acetate 0-50% ethyl acetate)
  10. additionProduct containing fractions
  11. concentrationconcentrated
  12. additionThe remaining oil was treated with hexanes
  13. concentrationconcentrated again

Sources & evidence

ORD record
ord-c87a5da94c654b62ba3222d140fb6954
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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