4-Nitrobenzenesulfonyl chloride → (R)-N-(2-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2-hydroxypropyl)-4-nitrobenzenesulfonamide

HRID 538364노트

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HRID 538364 반응식
Cl.[NH2:2][CH2:3][C@:4]([C:7]1[C:12]([F:13])=[C:11]([Si:14]([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:10]=[C:9]([Br:21])[N:8]=1)([OH:6])[CH3:5].C([O-])(O)=O.[Na+].[N+:27]([C:30]1[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=1)([O-:29])=[O:28]>C1COCC1.O>[Br:21][C:9]1[N:8]=[C:7]([C@@:4]([OH:6])([CH3:5])[CH2:3][NH:2][S:36]([C:33]2[CH:32]=[CH:31][C:30]([N+:27]([O-:29])=[O:28])=[CH:35][CH:34]=2)(=[O:37])=[O:38])[C:12]([F:13])=[C:11]([Si:14]([CH2:17][CH3:18])([CH2:19][CH3:20])[CH2:15][CH3:16])[CH:10]=1

참가 물질

6

반응물 3

HCID 74044-Nitrobenzenesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 86668070(R)-1-Amino-2-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-propan-2-ol hydrochloride

생성물 1

HCID 86668073(R)-N-(2-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2-hydroxypropyl)-4-nitrobenzenesulfonamide수율 62.8%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

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온도
2.5 °C

실험 절차

To a solution of crude (R)-1-amino-2-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-propan-2-ol hydrochloride (43.5 g, 109 mmol) in 335 ml THF was added a solution of NaHCO3 (21.02 g, 250 mmol) in 500 ml water. The mixture was cooled to 0-5° C. and a solution of 4-nitrobenzenesulfonyl chloride (26.5 g, 120 mmol) in 100 ml THF was added in a dropwise. The resulting emulsion was stirred overnight while allowing the temperature to reach rt. The mixture was extracted with TBME. The organic layer was dried with MgSO4.H2O, filtered and evaporated to give an orange resin which was purified on a silica gel column by eluting with Hexanes/10-20% EtOAc to yield 37.56 g of the title compound as a yellow resin. TLC (Hex/EtOAc 3/1) Rf=0.34; HPLC: RtH11=1.678 min; ESIMS: 548, 550 [(M+H)+, 1Br]; 1H-NMR (400 MHz, DMSO-d6): 8.40 (d, 2H), 8.06 (t, 1H), 7.97 (d, 2H), 7.45 (d, 1H), 5.42 (s, 1H), 3.23 (d, 2H), 1.44 (s, 3H) 0.97-0.81 (m, 15H); Chiral HPLC (Chiralpak AD-H 1213, UV 210 nm): 90% ee.

후처리

  1. customto reach rt
  2. extractionThe mixture was extracted with TBME
  3. dry with materialThe organic layer was dried with MgSO4.H2O
  4. filtrationfiltered
  5. customevaporated
  6. customto give an orange resin which
  7. customwas purified on a silica gel column
  8. washby eluting with Hexanes/10-20% EtOAc

출처 및 근거

ORD 기록
ord-809b5a9cdcb0456f80ab208bf551d7ad
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865712B2

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