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]2Participants
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/CH2 Cl2. Adamantoyl oxymethyl chloride was obtained by conversion of 1-adamantanecarbonyl chloride (Aldrich No. 11,772-2) with (CH2 O)n /ZnCl2 and has been described (Bodor, et al J Med Chem (1980) 23:474-480).
Workup
- customthe volatiles were removed under vacuum
- customThe crude product obtained
- customafter removal of the solvent
- washwashed with 3% MeOH/CH2Cl2
- customto remove nonpolar impurities
- wash1 g (30%) of bis(adamantoyl oxymethyl)PMEA ester was eluted in 8% MeOH/CH2 Cl2
Sources & evidence
- ORD record
- ord-a8a50f05b32742388077fbcfb5a298d8
- Source dataset
- uspto-grants-1998_02
- Patent number
- US05717095
Linked notes
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