Toluene → Diacetylacyclovir

HRID 865355Notes

Reaction equation

HRID 865355 reaction equation
[C:1]([O:4][CH2:5][CH2:6][O:7][CH2:8][N:9]1[CH:17]=[N:16][C:15]2[C:14](=[O:18])[NH:13][C:12]([NH2:19])=[N:11][C:10]1=2)(=[O:3])[CH3:2].C1(C)C=CC=CC=1.CCCCCC.[C:33](OC(=O)C)(=[O:35])[CH3:34]>CN(C)C1C=CN=CC=1>[C:1]([O:4][CH2:5][CH2:6][O:7][CH2:8][N:9]1[CH:17]=[N:16][C:15]2[C:14](=[O:18])[NH:13][C:12]([NH:19][C:33](=[O:35])[CH3:34])=[N:11][C:10]1=2)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 1140TolueneHCID 7918Acetic AnhydrideHCID 8058HexaneHCID 1354469309-(2-Acetoxyethoxymethyl)guanine

Product 1

HCID 135433881DiacetylacyclovirYield 79%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Conditions

Temperature
120 °C

Procedure

9-(2-Acetoxyethoxy)methylguanine (2 gms, 7.5 mmol) was dissolved in 15 ml of acetic anhydride. The mixture was heated to 120° C. and 0.1 gms (0.8 mmol) of 4-dimethylaminopyridine (DMAP) added. The reaction mixture was kept at 120° C. for 3 hours, then the mixture was cooled to 40° C. and 10 ml of toluene added. Hexane (20 ml) was added slowly to effect crystallization of the product. The solid was collected by filtration and washed with hexane, yielding 1.82 gms of 9-(2-acetoxyethoxy)methyl-N2 -acetylguanine (79%) with a N-9/N-7 isomer ratio of >200:1. Characteristic analytical data are as follows: 1H NMR (DMSO-d6) δ1.85 (3H, singlet, --NHCOCH3), 2.08 (3H, singlet, --O2CCH3) , 3.6 (2H, multiplet, --OCH2 --) , 3.95 (2H, multiplet, --CH2O--), 5.4 (2H, singlet, --NCH2O--) , 8.06 (1H, singlet, --N=CH--N--).

Workup

  1. temperaturethe mixture was cooled to 40° C.
  2. customcrystallization of the product
  3. filtrationThe solid was collected by filtration
  4. washwashed with hexane

Sources & evidence

ORD record
ord-6d5d82c9e0e94be183216192bbf38a9e
Source dataset
uspto-grants-1996_10
Patent number
US05565565

Reaction notes

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