2-Bromo-4-fluorobenzene-1-sulfonyl chloride → methyl (R)-7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate

HRID 715941Notes

Reaction equation

HRID 715941 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9](Cl)(=[O:11])=[O:10].[NH2:13][C:14]1[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:18]2[O:19][CH2:20][C@H:21]3[CH2:25][CH2:24][CH2:23][N:22]3[C:17]2=[CH:16][CH:15]=1>N1C=CC=CC=1.C(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:13][C:14]1[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:18]2[O:19][CH2:20][C@H:21]3[CH2:25][CH2:24][CH2:23][N:22]3[C:17]2=[CH:16][CH:15]=1)(=[O:11])=[O:10]

Participants

5

Reactant 2

HCID 27782162-Bromo-4-fluorobenzene-1-sulfonyl chlorideHCID 86712109methyl (R)-7-amino-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate2×

Product 1

HCID 71003749methyl (R)-7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylateYield 79.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

2-Bromo-4-fluorobenzenesulfonyl chloride (0.656 g) was added to a solution of methyl (R)-7-amino-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (Intermediate 6, 0.525 g) in pyridine (10 mL) and DCM (10 mL) and the mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and 0.5M hydrochloric acid solution. 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 a pale yellow solid which was triturated with ether and cyclohexane (1:2) to give methyl (R)-7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (0.820 g).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate and 0.5M hydrochloric acid solution
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by chromatography on silica
  7. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-40%
  8. customto give a pale yellow solid which
  9. customwas triturated with ether and cyclohexane (1:2)

Sources & evidence

ORD record
ord-0eb1669ab3fb468ba990eaea060b0e05
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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