Dimethylformamide → 1-Adamantanecarbonyl chloride

HRID 1976268Notes

Reaction equation

HRID 1976268 reaction equation
[CH2:1]1[CH2:11][CH2:10]N2[C:4](=NCCC2)[CH2:3][CH2:2]1.C1N=[C:16](N)[C:15]2N=CN(CCOCP(O)(O)=O)[C:14]=2N=1.[C:30]12([C:40]([O:42][CH2:43][Cl:44])=[O:41])[CH2:39][CH:34]3[CH2:35][CH:36]([CH2:38][CH:32]([CH2:33]3)[CH2:31]1)[CH2:37]2.[CH3:45]N(C=O)C>>[C:30]12([C:40]([O:42][CH2:43][Cl:44])=[O:41])[CH2:39][CH:34]3[CH2:33][CH:32]([CH2:38][CH:36]([CH2:35]3)[CH2:37]1)[CH2:31]2.[C:11]12([C:43]([Cl:44])=[O:42])[CH2:10][CH:4]3[CH2:3][CH:2]([CH2:14][CH:15]([CH2:16]3)[CH2:45]1)[CH2:1]2

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 60172AdefovirHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 14699931Adamantoyl oxymethyl chloride

Product 2

HCID 989151-Adamantanecarbonyl chlorideHCID 14699931Adamantoyl oxymethyl chloride

Procedure

DBU (1,8-diazabicyclo[5.4.0]undec-7-ene; 1.53 g, 10 mmol) was added to a suspension of PMEA (1.365 g, 5 mmol) in DMF (25 mL). Adamantoyl oxymethyl chloride (5.72 g, 25 mmol) in DMF (25 mL) was added to the reaction mixture which was then stirred for four days at room temperature and the volatiles were removed under vacuum. The crude product obtained after removal of the solvent was loaded onto a silica gel column and washed with 3% MeOH/CH2Cl2 to remove nonpolar impurities. 1 g (30%) of bis(adamantoyl oxymethyl)PMEA ester was eluted in 8% MeOH/CH2Cl2. Adamantoyl oxymethyl chloride was obtained by conversion of 1-adamantanecarbonyl chloride (Aldrich No. 11,772-2) with (CH2O)n/ZnCl2 and has been described (Bodor, et al J Med Chem (1980) 23:474-480).

Workup

  1. customthe volatiles were removed under vacuum
  2. customThe crude product obtained
  3. customafter removal of the solvent
  4. washwashed with 3% MeOH/CH2Cl2
  5. customto remove nonpolar impurities
  6. wash1 g (30%) of bis(adamantoyl oxymethyl)PMEA ester was eluted in 8% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-6fe7a3351b0945b99c91c3d4890d9fc0
Source dataset
uspto-grants-2001_05
Patent number
US06225460B1

Reaction notes

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