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

Participants

Role	Name	HCID	Charge
Reactant	Ethylene Glycol	HCID 174	—
Reactant	p-Toluenesulfonic acid monohydrate	HCID 521998	—
Reactant	N-benzyloxycarbonyl-2(R,S)-formyl-3,4-dihydro-2H-1,4-benzoxazine	HCID 19697651	—
Reactant	5(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	HCID 131720526	—
Solvent	Water	HCID 962	—
Solvent	Toluene	HCID 1140	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	N-benzyloxycarbonyl-2(R,S)-(dioxolan2-yl)-3,4-dihydro-2H-1,4-benzoxazine	HCID 19697620	—

Reaction Steps

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.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US05719141
Source dataset	uspto-grants-1998_02
ORD ID	ord-c9c570d0673347348d45097e46a7049f
Source note	uspto-grants-1998_02