Cesium carbonate → methyl (R)-7-amino-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate

HRID 715945Notes

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([O:12][CH2:13][C@H:14]2[CH2:18][CH2:17][CH2:16][NH:15]2)[C:5](Br)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]2[O:12][CH2:13][C@H:14]3[CH2:18][CH2:17][CH2:16][N:15]3[C:5]2=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of methyl 6-amino-3-bromo-2-((R)-1-pyrrolidin-2-ylmethoxy)benzoate (Intermediate 7, 1.65 g), palladium acetate (0.281 g), (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (1.56 g) and cesium carbonate (3.26 g) in toluene (40 mL) was heated at 100° C., under an atmosphere of nitrogen for 2 hours. The mixture was cooled and partitioned between ethyl acetate and water. The organic layer was dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-40% to give methyl (R)-7-amino-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (0.528 g) as a dark oil.

Workup

temperatureThe mixture was cooled
custompartitioned between ethyl acetate and water
dry with materialThe organic layer was dried (Na2SO4)
filtrationfiltered
concentrationthe filtrate was concentrated in vacuo
customThe residue was purified by chromatography on silica
washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-40%

Sources & evidence

ORD record: ord-e1102cbdca9b40d68f3bebddc0a5e78c
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187494B2

Reaction notes

Loading…