Hydrochloric Acid → 9-{3-[2-(Hydroxymethyl)pyrimidin-4-yl]-6-methoxy-2-methylphenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione

HRID 873550Notes

Reaction equation

HRID 873550 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][N:24]=[C:23]([C:27](O)=[O:28])[N:22]=2)=[C:17]([CH3:30])[C:16]=1[CH:31]1[C:44]2[C:43](=[O:45])[CH2:42][C:41]([CH3:47])([CH3:46])[CH2:40][C:39]=2[O:38][C:37]2[CH2:36][C:35]([CH3:49])([CH3:48])[CH2:34][C:33](=[O:50])[C:32]1=2.[BH4-].[Na+].Cl>C1COCC1.O.CN(C=O)C>[OH:28][CH2:27][C:23]1[N:22]=[C:21]([C:18]2[C:17]([CH3:30])=[C:16]([CH:31]3[C:44]4[C:43](=[O:45])[CH2:42][C:41]([CH3:46])([CH3:47])[CH2:40][C:39]=4[O:38][C:37]4[CH2:36][C:35]([CH3:49])([CH3:48])[CH2:34][C:33](=[O:50])[C:32]3=4)[C:15]([O:14][CH3:13])=[CH:20][CH:19]=2)[CH:26]=[CH:25][N:24]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 4311764Sodium borohydrideHCID 1177005224-[4-Methoxy-2-methyl-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyrimidine-2-carboxylic acid

Product 1

HCID 1177009029-{3-[2-(Hydroxymethyl)pyrimidin-4-yl]-6-methoxy-2-methylphenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dioneYield 57.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

1,1′-Carbonyldiimidazole (33.9 mg, 0.209 mol) was added to a suspension of the 4-[4-methoxy-2-methyl-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyrimidine-2-carboxylic acid obtained in Example 75-4 (90.0 mg, 0.174 mmol) in THF (2.0 mL) at room temperature, and the mixture thus obtained was then stirred at 50° C. for 1.5 hours. Thereafter, DMF (0.5 mL) was added to the resulting solution, and the mixture thus obtained was further stirred at the same temperature as above for 20 minutes. Subsequently, the reaction solution was cooled to 0° C., and sodium borohydride (13.2 mg, 0.348 mmol) and water (0.1 mL) were then added to the reaction solution. The mixture thus obtained was stirred at room temperature for 30 minutes. Thereafter, water and 1 M-hydrochloric acid were added to the reaction solution, and the mixed solution was then extracted with ethyl acetate twice. The organic layer thus obtained was washed with brine, and was then dried over anhydrous sodium sulfate. After that, the solvent was distilled away under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (dichloromethane:methanol=1:0 to 10:1, v/v), and was then solidified with diethyl ether to obtain the title compound (49.9 mg, yield: 56%).

Workup

  1. customthe mixture thus obtained
  2. customthe mixture thus obtained
  3. stirringwas further stirred at the same temperature as above for 20 minutes
  4. temperatureSubsequently, the reaction solution was cooled to 0° C.
  5. customThe mixture thus obtained
  6. stirringwas stirred at room temperature for 30 minutes
  7. extractionthe mixed solution was then extracted with ethyl acetate twice
  8. customThe organic layer thus obtained
  9. washwas washed with brine
  10. dry with materialwas then dried over anhydrous sodium sulfate
  11. distillationAfter that, the solvent was distilled away under reduced pressure
  12. customThe residue thus obtained
  13. customwas purified by silica gel column chromatography (dichloromethane

Sources & evidence

ORD record
ord-bb33c155ed8f4a08b807fee857ef1586
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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