Tetrahydrofuran → HCID 90373050, compound

HRID 930343Notes

Reaction equation

HRID 930343 reaction equation
[Br:1][C:2]1[N:7]=[C:6](/[C:8](=[N:11]\[S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])/[CH2:9][F:10])[C:5]([F:18])=[C:4]([Si:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[CH:3]=1.C1COCC1.[Cl-].[C:32]([O:36][C:37](=[O:40])[CH2:38][Zn+])([CH3:35])([CH3:34])[CH3:33]>C([O-])(O)=O.[Na+].O>[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:11][S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])([CH2:9][F:10])[CH2:38][C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:40])[C:5]([F:18])=[C:4]([Si:19]([CH2:20][CH3:21])([CH2:22][CH3:23])[CH2:24][CH3:25])[CH:3]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 90373278HCID 90373278, compoundHCID 178451183HCID 178451183, compound

Product 1

HCID 90373050HCID 90373050, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a 1000 mL 3-neck round-bottomed flask equipped with an addition funnel and internal temperature probe was added (R,E)-N-(1-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2-fluoroethylidene)-2-methylpropane-2-sulfinamide (43.3 g, 95 mmol) and THF (400 mL). The mixture was cooled to 0° C. and 2-tert-butoxy-2-oxoethylzinc chloride (Rieke Metals; 458 mL, 229 mmol, 0.5 M in diethyl ether) was added dropwise over 1 h keeping the internal temperature under 3° C. After the addition the ice bath was allowed to melt and warm to rt overnight. The reaction mixture was diluted with sat NaHCO3 (200 mL) and water (200 mL) and extracted with EtOAc (3×200 mL). The combined extracts were washed with brine, dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (Gradient: 0.0 to 25% EtOAc/hexane, 1500 g RediSep column) afforded:

Workup

  1. customTo a 1000 mL 3-neck round-bottomed flask equipped with an addition funnel
  2. customunder 3° C
  3. temperaturewarm to rt overnight
  4. extractionextracted with EtOAc (3×200 mL)
  5. washThe combined extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated onto silica
  8. customPurification by silica gel chromatography (Gradient: 0.0 to 25% EtOAc/hexane, 1500 g RediSep column)
  9. customafforded

Sources & evidence

ORD record
ord-352743dc9f964be1813d1a18f4b75d7b
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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