Water → Methyl 3-hydroxy-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate

HRID 1372219Notes

Reaction equation

HRID 1372219 reaction equation
CO[C:3](=[O:20])[CH2:4][C:5]1([C:16]([O:18][CH3:19])=[O:17])O[N:12]2[C:7]([C:8]([CH3:15])([CH3:14])[O:9][CH2:10][CH2:11]2)=[N:6]1.[OH2:21]>CC1C=CC(C)=CC=1C>[OH:21][C:4]1[C:3](=[O:20])[N:12]2[C:7]([C:8]([CH3:14])([CH3:15])[O:9][CH2:10][CH2:11]2)=[N:6][C:5]=1[C:16]([O:18][CH3:19])=[O:17]

Participants

4

Reactant 2

HCID 962WaterHCID 21069965Methyl 2-(2-methoxy-2-oxoethyl)-8,8-dimethyl-2,5,6,8-tetrahydro-[1,2,4]oxadiazolo[3,2-c][1,4]oxazine-2-carboxylate

Product 1

HCID 54708350Methyl 3-hydroxy-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 72471,2,4-TrimethylbenzeneSolvent

Conditions

Temperature
10 °C

Procedure

A solution of the above crude methyl 2-(2-methoxy-2-oxoethyl)-8,8-dimethyl-2,5,6,8-tetrahydro-[1,2,4]oxadiazolo[3,2-c][1,4]oxazine-2-carboxylate (8.34 g) in 1,2,4-trimethylbenzene (80 mL) was heated at 155° C. for 9 h. The resulting dark mixture was cooled to 20–25° C. and diluted with water (50 mL). The product was extracted into 0.5M Na2CO3 (2×50 mL). The organic layer was discarded. The aqueous phases were combined and washed with CH2Cl2 (40 mL). The organic wash was discarded. The aqueous solution was acidified to pH 2.0 with 6M sulfuric acid (9.0 mL) and the product extracted into CH2Cl2 (2×20 mL). The combined CH2Cl2 layers were evaporated in vacuo. The residue was redissolved in isopropanol (75 mL) at 75° C. and the solution was treated with activated charcoal (0.85 g) at 75–80° C. for 20 min. The charcoal was removed by filtration and washed with hot isopropanol. The combined filtrate and wash was concentrated in vacuo to 40 mL. The resulting slurry was cooled slowly with stirring to 10° C. and stirred for 1 h. The solid was filtered, washed with cold isopropanol (10 mL) and dried in vacuo at 40–45° C. to afford methyl 3-hydroxy-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate as an off-white crystalline solid (3.68 g).

Workup

  1. temperatureThe resulting dark mixture was cooled to 20–25° C.
  2. extractionThe product was extracted into 0.5M Na2CO3 (2×50 mL)
  3. washwashed with CH2Cl2 (40 mL)
  4. washThe organic wash
  5. extractionthe product extracted into CH2Cl2 (2×20 mL)
  6. customThe combined CH2Cl2 layers were evaporated in vacuo
  7. dissolutionThe residue was redissolved in isopropanol (75 mL) at 75° C.
  8. additionthe solution was treated with activated charcoal (0.85 g) at 75–80° C. for 20 min
  9. customThe charcoal was removed by filtration
  10. washwashed with hot isopropanol
  11. washThe combined filtrate and wash
  12. concentrationwas concentrated in vacuo to 40 mL
  13. temperatureThe resulting slurry was cooled slowly
  14. stirringstirred for 1 h
  15. filtrationThe solid was filtered
  16. washwashed with cold isopropanol (10 mL)
  17. customdried in vacuo at 40–45° C.

Sources & evidence

ORD record
ord-02c62af76bcf4562bc77fec94740bb9e
Source dataset
uspto-grants-2007_01
Patent number
US07157447B2

Reaction notes

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