2-Bromo-4-fluorobenzene-1-sulfonyl chloride → methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate

HRID 595111Notes

Reaction equation

HRID 595111 reaction equation
[NH2:1][C:2]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:6]2[O:7][CH2:8][CH:9]3[CH:13]=[CH:12][CH2:11][N:10]3[C:5]2=[CH:4][CH:3]=1.[Br:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[S:27](Cl)(=[O:29])=[O:28]>C(Cl)Cl.N1C=CC=CC=1>[Br:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[S:27]([NH:1][C:2]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:6]2[O:7][CH2:8][C:9]3[N:10]([CH:11]=[CH:12][CH:13]=3)[C:5]2=[CH:4][CH:3]=1)(=[O:29])=[O:28]

Participants

5

Reactant 2

HCID 27782162-Bromo-4-fluorobenzene-1-sulfonyl chlorideHCID 86712820Methyl 7-amino-3a,4-dihydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate2×

Product 1

HCID 70983589methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylateYield 14.8%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl 7-amino-3a,4-dihydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (Intermediate 17, 0.370 g) was suspended in a mixture of DCM (6 mL) and pyridine (2.43 mL) and 2-bromo-4-fluorobenzenesulfonyl chloride (0.493 g) was added. The resultant deep red solution was stirred at room temperature overnight then concentrated in vacuo. The residue was diluted with DCM and water and passed through a phase separator. The organic layer was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-30% to give methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (0.107 g) as a white solid.

Workup

  1. additionwas added
  2. concentrationthen concentrated in vacuo
  3. additionThe residue was diluted with DCM and water
  4. concentrationThe organic layer was concentrated in vacuo
  5. customthe residue was purified by chromatography on silica
  6. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-30%

Sources & evidence

ORD record
ord-b149553c172a4e3684a3369b97c95f14
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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