2-Methyl-2-butene → 5-benzyloxycarbonylamino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-ylacetic acid

HRID 1744232Notes

Reaction equation

HRID 1744232 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:17](=[O:18])[N:16]([CH2:19][CH:20]=[O:21])[C:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(=CC)C.Cl([O-])=[O:34].[Na+].O.P([O-])(O)(O)=O.[Na+]>O1CCCC1.C(O)(C)(C)C.O.[Au]>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:17](=[O:18])[N:16]([CH2:19][C:20]([OH:34])=[O:21])[C:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 10361338Benzyl [6-oxo-1-(2-oxoethyl)-2-phenyl-1,6-dihydropyrimidin-5-yl]carbamateHCID 23668197Sodium Chlorite

Product 1

HCID 102491135-benzyloxycarbonylamino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-ylacetic acidYield 88%

Reagents, catalysts & solvents 4

HCID 23985GoldCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of crude [5-[(benzyloxycarbonyl)amino]-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl]acetaldehyde (15.30 g, 42.11 mmol) in 198.0 mL of tetrahydrofuran, t-butyl alcohol, and 2-methyl-2-butene (1:1:1.3, 0.21 M) was cooled to 0° C. The solution was then slowly added a solution of sodium chlorite (29.94 g, 331.1 mmol) and sodium dihydrogenphosphate monohydrate (35.42 g, 256.7 mmol) in 102.0 mL of water (3.2 M based on sodium chlorite). The resulting gold colored, biphasic solution was stirred for 10 minutes and the cold bath was removed. The reaction was stirred for 1 hour at room temperature. The volatiles were removed under reduced pressure. The resulting solution was diluted with water (200 mL) and the pH was adjusted to 3 by addition of sat NaHCO3 and 1N HCl. The aqueous solution was extracted by tetrahydrofuran, dichloromethane (1:2, 4×180 mL). The combined organic solutions were dried (MgSO4), filtered, and concentrated to give the crude product. Purification by trituration with ethyl ether gave an 88% yield of [5[(benzyloxycarbonyl)amino]-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl]acetic acid as a white solid: 1H NMR (300 MHz, d-DMSO) δ 13.34 (br s, 1H), 9.03 (s, 1H), 7.57–7.34 (m, 10H), 5.23 (s, 2H), 4.56 (s, 2H); 13C NMR (75 MHz, d-DMSO) δ 169.4, 158.0, 154.6, 154.3, 137.1, 134.8, 130.9, 129.4, 129.1, 128.78, 128.72, 128.50, 125.5, 67.0, 48.8; HRMS (EI) calcd for C20H18N3O5 380.1246, found 380.1246.

Workup

  1. customthe cold bath was removed
  2. stirringThe reaction was stirred for 1 hour at room temperature
  3. customThe volatiles were removed under reduced pressure
  4. additionThe resulting solution was diluted with water (200 mL)
  5. additionthe pH was adjusted to 3 by addition of sat NaHCO3 and 1N HCl
  6. extractionThe aqueous solution was extracted by tetrahydrofuran, dichloromethane (1:2, 4×180 mL)
  7. dry with materialThe combined organic solutions were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude product
  11. customPurification by trituration with ethyl ether

Sources & evidence

ORD record
ord-d04fd335f87e43acb70a7002bce7012e
Source dataset
uspto-grants-2006_03
Patent number
US07015223B1

Reaction notes

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