Water → methyl 3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxylate

HRID 1871038Notes

Reaction equation

HRID 1871038 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[NH:7][C:8]2[C:13]([C:14]=1[C:15]([O:17][CH3:18])=[O:16])=[CH:12][CH:11]=[CH:10][CH:9]=2.[OH-].[Na+].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[O:5]1[C:6]2=[C:14]([C:15]([O:17][CH3:18])=[O:16])[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]2[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 3

HCID 962Water2×HCID 14798Sodium HydroxideHCID 9816818Methyl 2-(3-chloropropoxy)indole-3-carboxylate

Product 1

HCID 11746477methyl 3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxylate

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
55 °C

Procedure

Method C A mixture of methyl 2-(3-chloropropoxy)-indole-3-carboxylate (100 g, 0.37 mol), aqueous sodium hydroxide solution (38 ml, 10.8M, 0.41 mol), water (38 ml) and tetrabutylammonium bromide (6.0 g, 0.019 mol) in toluene (1000 ml) was stirred at 50-60° C. for about one hour. Water (120 ml) was added and the aqueous layer was removed. The organic layer was washed with water (120 ml) and dried by azeotropic distillation of toluene (250 m) giving a dry solution of methyl 3,4-dihydro-2H-[1,3]-oxazino[3,2-a]indole-10-carboxylate in toluene. This solution was cooled to ambient temperature and treated sequentially with a solution of 1-butyl-4-piperidinylmethylamine (66.8 g, 0.39 mol) in toluene (200 ml) followed by a solution of trimethylaluminium in toluene (196 ml, 2.0M, 0.39 mol). The mixture was heated to reflux and stirred for three hours. The reaction was quenched by cautious addition of aqueous sodium hydroxide solution (460 ml, 10% w/v) and then washed once with aqueous sodium hydroxide solution (460 ml, 10% w/v) and twice with water (275 ml each wash) while maintaining the temperature at about 70° C. Toluene (200 ml) was added and the resulting solution was dried by azeotropic distillation of toluene (200 ml) at about 55° C. under reduced pressure. Hexane (1400 ml) was added and the resulting slurry cooled to about 0-5° C. for about one hour. The solid was isolated by filtration and dried in vacuo to give the product, N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]-oxazino[3,2-a]indole-10-carboxamide, (114.7 g, 83%) as a white crystalline solid.

Workup

  1. customthe aqueous layer was removed
  2. washThe organic layer was washed with water (120 ml)
  3. dry with materialdried by azeotropic distillation of toluene (250 m)

Sources & evidence

ORD record
ord-facb113027f944febb650b251e092508
Source dataset
uspto-grants-2000_08
Patent number
US06100397

Reaction notes

Loading…