Acetic Acid → HCID 10608894, compound

HRID 1415316Notes

Reaction equation

HRID 1415316 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[CH:3][CH:2]1[C:11]([O:13][CH2:14][CH3:15])=[O:12].C=O.[C:18]([BH3-])#N.[Li+].C(O)(=O)C>C(#N)C.C(OCC)C>[CH3:18][N:4]1[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[O:1][C:2]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:3]1

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 712FormaldehydeHCID 53880241HCID 53880241, compoundHCID 13171016319536-84-6

Product 1

HCID 10608894HCID 10608894, compoundYield 95.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

Ethyl 1,4-benzoxazine-2-carboxylate (5.8g.) was dissolved in acetonitrile (15ml.) under an atmosphere of argon. Formaldehyde (30ml. of a 37% aqueous solution) and lithium cyanoborohydride (4.67g.) were added, and the solution was stirred for 5 minutes. Glacial acetic acid (3.5ml.) was added dropwise and over a period of 10 minutes, and the solution was stirred at room temperature for 2 hours. More glacial acetic acid (3.5ml.) was added, and after 30 minutes the reaction mixture was poured into diethyl ether (200ml.), washed successively with 0.1N hydrochloric acid, sodium bicarbonate and brine, and was dried. The solvent was evaporated to give the crude 2-carboxyethyl-4-methyl-1,4-benzoxazine, which was purified by chromatography on silica gel (148g.). Elution with 10% ethyl acetate in toluene gave pure ethyl 4-methyl-1,4-benzoxazine-2-carboxylate (5.9g.) whose n.m.r. spectrum in deuteriochloroform showed the following features (δ values):

Workup

  1. stirringthe solution was stirred at room temperature for 2 hours
  2. washwashed successively with 0.1N hydrochloric acid, sodium bicarbonate and brine
  3. customwas dried
  4. customThe solvent was evaporated
  5. customto give the crude 2-carboxyethyl-4-methyl-1,4-benzoxazine, which
  6. customwas purified by chromatography on silica gel (148g.)
  7. washElution with 10% ethyl acetate in toluene

Sources & evidence

ORD record
ord-20d31df65a5542b28e649eb775fa2740
Source dataset
uspto-grants-1977_01
Patent number
US04004021

Reaction notes

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