tert-Butyl hydroperoxide → Phosphoric acid dibenzyl ester 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl ester

HRID 480134Notes

Reaction equation

HRID 480134 reaction equation
[OH:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]3[NH:18][C:17]4[C:16](=[O:19])[N:15]([CH2:20][CH2:21][CH3:22])[C:14](=[O:23])[N:13]([CH2:24][CH2:25][CH3:26])[C:12]=4[N:11]=3)([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.N1C=NN=N1.C(N(CC)[P:35]([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)C.C([O:58]O)(C)(C)C.OS([O-])=O.[Na+]>C(#N)C.C(Cl)Cl>[O:23]=[C:14]1[N:13]([CH2:24][CH2:25][CH3:26])[C:12]2[N:11]=[C:10]([C:5]34[CH2:8][CH2:9][C:2]([O:1][P:35](=[O:58])([O:36][CH2:37][C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=5)[O:44][CH2:45][C:46]5[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=5)([CH2:7][CH2:6]3)[CH2:3][CH2:4]4)[NH:18][C:17]=2[C:16](=[O:19])[N:15]1[CH2:20][CH2:21][CH3:22]

Participants

8

Reactant 5

HCID 6410tert-Butyl hydroperoxideHCID 5066231Dibenzyl diethylphosphoramiditeHCID 99507768-(4-hydroxybicyclo[2.2.2]octan-1-yl)-1,3-dipropyl-1H-purine-2,6(3H,7H)-dioneHCID 23665763Sodium BisulfiteHCID 178418441HCID 178418441, compound

Product 1

HCID 67078989Phosphoric acid dibenzyl ester 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl ester

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

8-(4-Hydroxy-bicyclo[2.2.2]oct-1-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione (Example 13a) (180 mg, 0.5 mmol) was dissolved in a mixture of 1H-tetrazole (350 mg, 5 mmol) in 10 ml of dry acetonitrile and 10 ml of dry methylene chloride. At room temperature dibenzyl diethylphosphoramidite (476 mg, 1.5 mmol) was added under nitrogen and the mixture was stirred for 2 h. Then 70% tert-butyl hydroperoxide solution (1 ml) was added and the mixture was stirred for 1 h. At 0° C. 15 ml of 10% NaHSO3 was added and the mixture was stirred for another 15 minutes. The mixture was then extracted three times with CH2Cl2, and the organic layer was washed water. Evaporation of solvent yielded Phosphoric acid dibenzyl ester 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl ester as a yellow oil, which was purified by column chromatography. Fractions contained Phosphoric acid dibenzyl ester 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl ester was combined and concentrated in vacuum to get 280 mg product. MS (M+1) 621.

Workup

  1. stirringthe mixture was stirred for 1 h
  2. customAt 0° C
  3. stirringthe mixture was stirred for another 15 minutes
  4. extractionThe mixture was then extracted three times with CH2Cl2
  5. washthe organic layer was washed water
  6. customEvaporation of solvent

Sources & evidence

ORD record
ord-c6dc90372af445b592a158f9c8058d5e
Source dataset
uspto-grants-2003_11
Patent number
US06649600B1

Reaction notes

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