Benzyl Bromide → ethyl 4-benzyl-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate

HRID 1448467Notes

Reaction equation

Cl.[CH2:2]([O:4][C:5]([CH:7]1[CH2:12][NH:11][C:10]2[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=2[O:8]1)=[O:6])[CH3:3].C(=O)(O)[O-].[Na+].[O-]CC.[Tl+].[CH2:26](Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>>[CH2:26]([N:11]1[C:10]2[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=2[O:8][CH:7]([C:5]([O:4][CH2:2][CH3:3])=[O:6])[CH2:12]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

Reactant 4

HCID 7498Benzyl Bromide

HCID 30143Ethanol, thallium(1+) salt

HCID 516892Sodium Bicarbonate

HCID 509988643,4-Dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid ethyl ester hydrochloride

Product 1

HCID 10542027ethyl 4-benzyl-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate

Procedure

1A was treated with sodium bicarbonate to prepare the free base (1B). A mixture of 5.3 g of 1B and 8.23 g of thallium ethoxide in 50 ml of dimethylformide was stirred at room temperature for 16 hours. 5.64 g of benzyl bromide then was added and the resulting mixture was stirred at room temperature for 5 hours. Thallium bromide precipitated and was filtered. The filtrate was stripped of solvent under reduced pressure and the residue was dry column chromatographed through silica gel using a 4:16:80 by volume mixture of tetrahydrofuran, ethyl acetate and hexane as eluent. The product was recrystallized from ether/hexane to give 1, as a solid, m.p.: 83.5°-84.5°.

Workup

stirringthe resulting mixture was stirred at room temperature for 5 hours
customThallium bromide precipitated
filtrationwas filtered
customthe residue was dry column
customchromatographed through silica gel using a 4:16:80
additionby volume mixture of tetrahydrofuran, ethyl acetate and hexane as eluent
customThe product was recrystallized from ether/hexane
customto give 1

Sources & evidence

ORD record: ord-f8ff67e3f0304a23b6e36b4db31d5669
Source dataset: uspto-grants-1979_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04180572

Reaction notes

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