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Ethylene Glycol → N-benzyloxycarbonyl-2(R,S)-(dioxolan2-yl)-3,4-dihydro-2H-1,4-benzoxazine

HRID 863307
Notes
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Reaction equation

HRID 863307 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]=1
ParticipantsProcedureSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 174Ethylene GlycolHCID 521998p-Toluenesulfonic acid monohydrateHCID 19697651N-benzyloxycarbonyl-2(R,S)-formyl-3,4-dihydro-2H-1,4-benzoxazineHCID 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)amide

Product 1

HCID 19697620
N-benzyloxycarbonyl-2(R,S)-(dioxolan2-yl)-3,4-dihydro-2H-1,4-benzoxazine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

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
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05719141

Reaction notes

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