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

HRID 538364Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 538364
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

Komponenten

6

Edukt 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

Produkt 1

HCID 86668073(R)-N-(2-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2-hydroxypropyl)-4-nitrobenzenesulfonamideAusbeute 62,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-809b5a9cdcb0456f80ab208bf551d7ad
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865712B2

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