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 715941노트

반응식

HRID 715941 반응식
[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]

참가 물질

5

반응물 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-carboxylate2회

생성물 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-carboxylate수율 79.9%

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-0eb1669ab3fb468ba990eaea060b0e05
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187494B2

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