Ethylene Glycol → N-benzyloxycarbonyl-2(R,S)-(dioxolan2-yl)-3,4-dihydro-2H-1,4-benzoxazine
Reaction equation
C(NC(=O)[C@H](C)C[C@H](O)[C@@H](N)CC(C)(C)C[C:14]([N:16]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[O:19][CH:18]([CH:26]2[O:30][CH2:29][CH2:28][O:27]2)[CH2:17]1)=[O:15])CCC.[CH2:37]([O:44]C(N1C2C=CC=CC=2OC(C=O)C1)=O)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(O)CO.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[CH2:37]([O:44][C:14]([N:16]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[O:19][CH:18]([CH:26]2[O:27][CH2:28][CH2:29][O:30]2)[CH2:17]1)=[O:15])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1Participants
Reactant 4
HCID 174Ethylene Glycol
HCID 521998p-Toluenesulfonic acid monohydrate
HCID 19697651N-benzyloxycarbonyl-2(R,S)-formyl-3,4-dihydro-2H-1,4-benzoxazine
HCID 1317205265(S)-Amino-4(S)-hydroxy-2(R),7,7-trimethyl-8-[2(R,S)-(dioxolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazin-4-ylcarbonyl]-octanoic acid (N-butyl)amideProduct 1
Reagents, catalysts & solvents 3
Procedure
The 2(R,S)-(dioxolan2-yl)-3,4-dihydro-2H-1,4-benzoxazine employed as the starting material is prepared by reaction of 500 mg of N-benzyloxycarbonyl-2(R,S)-formyl-3,4-dihydro-2H-1,4-benzoxazine (Example 107)with 0.28 ml of ethylene glycol in 25 ml of toluene under reflux, with azeotropic removal of water, overnight in the presence of 25 mg of p-toluenesulfonic acid hydrate. After customary working up and FC of the crude product over silica gel with a 6:1 mixture of toluene and ethyl acetate, N-benzyloxycarbonyl-2(R,S)-(dioxolan2-yl)-3,4-dihydro-2H-1,4-benzoxazine is obtained (Rf- (3:1 mixture of toluene and ethyl acetate)=0.52). Subsequent hydrogenolysis analogously to Example 1r) gives 2(R,S)-(dioxolan2-yl)-3,4-dihydro-2H-1,4-benzoxazine: Rf (P)=0.74; FAB-MS: (M+H)+ =208.
Sources & evidence
- ORD record
- ord-c9c570d0673347348d45097e46a7049f
- Source dataset
- uspto-grants-1998_02
- Patent number
- US05719141
Reaction notes
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