Pyrimidine → 5-(Benzyloxy)-1,2-dimethyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid

HRID 2238472Notes

Reaction equation

HRID 2238472 reaction equation
N1C=CC=NC=1.[CH3:7][C:8]1[N:13]([CH3:14])[C:12](=[O:15])[C:11]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:10]([CH2:24][OH:25])[N:9]=1.[Na+].[Br-].[OH-:28].[Na+]>CC1(C)N([O])C(C)(C)CCC1.CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].C(Cl)Cl.O>[CH3:7][C:8]1[N:13]([CH3:14])[C:12](=[O:15])[C:11]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:10]([C:24]([OH:28])=[O:25])[N:9]=1

Participants

9

Reactant 4

HCID 9260PyrimidineHCID 14798Sodium HydroxideHCID 253881Sodium BromideHCID 225948722,3-Dimethyl-5-benzyloxy-6-(hydroxymethyl)-4-pyrimidinone

Product 1

HCID 225948875-(Benzyloxy)-1,2-dimethyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acidYield 54.9%

Reagents, catalysts & solvents 4

HCID 21218Trioctylmethylammonium chlorideCatalystHCID 2724126TempoCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The above pyrimidine, 32 (9.00 g, 34.6 mmol), TEMPO catalyst (55 mg), Adogen-464 phase transfer catalyst (690 mg) and NaBr (360 mg, 3.50 mmol) were combined in CH2Cl2 (400 mL) and water (10 mL). After cooling to 0° C. the reaction was stirred at 1500 r.p.m. while adding a cooled (10° C.) buffered bleach solution (125 mL commercial bleach+125 mL water +12.5 g NaHCO3) keeping the reaction <4° C. (takes approx. 15 min). After a further 5 min, 2M NaOH solution was added until a solution of pH 10 was obtained. The CH2Cl2 layer was separated and extracted with basic water (pH 10, 100 mL). The combined aqueous solutions were washed with CH2Cl2 (50 mL). The aqueous phase was concentrated to ˜200-250 mL and carefully acidified (conc. HCl) to pH 2, concomitant with precipitation. After standing at 5° C. overnight the white solid was filtered, washed with water and dried under high vacuum to give 5.20 g (54.9%) of 33. Mp: 180-181° C. (+)FABMS: m/z 275. 1H NMR (CDCl3, 300 MHz): δ 2.53 (s, 3H, 2-Me), 3.55 (s, 3H, N-Me), 5.46 (s, 2H, BnCH2), 7.30-7.38 (m, 3H, Ph), 7.49-7.52 (m, 2H, Ph). 13C NMR (DMSO-d6, 100 MHz): δ 22.6, 31.2 73.3, 128.0, 128.2, 128.3, 136.9, 139.1, 143.0, 155.7, 159.2, 165.7. Anal. Calcd (found) for C14H14N2O4: C, 61.31(61.36); H, 5.14 (5.06); N, 10.21(10.30).

Workup

  1. additionwhile adding
  2. temperaturea cooled (10° C.)
  3. customthe reaction <4° C. (takes approx. 15 min)
  4. customwas obtained
  5. customThe CH2Cl2 layer was separated
  6. extractionextracted with basic water (pH 10, 100 mL)
  7. washThe combined aqueous solutions were washed with CH2Cl2 (50 mL)
  8. concentrationThe aqueous phase was concentrated to ˜200-250 mL
  9. customwith precipitation
  10. waitAfter standing at 5° C. overnight
  11. filtrationthe white solid was filtered
  12. washwashed with water
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-c1486089cb1146c8a713d7c28561fa05
Source dataset
uspto-grants-2010_05
Patent number
US07718781B2

Reaction notes

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