1,2-Dibromo-1,1,2,2-tetrafluoroethane → 2-Bromo-6-(3-methoxy-4-triisopropylsilanyloxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one

HRID 2384883Notes

Reaction equation

HRID 2384883 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:20]2[CH2:25][CH2:24][C:23]3[CH:26]=[CH:27][S:28][C:22]=3[C:21]2=[O:29])[CH:6]=[CH:7][C:8]=1[O:9][Si:10]([CH:17]([CH3:19])[CH3:18])([CH:14]([CH3:16])[CH3:15])[CH:11]([CH3:13])[CH3:12].C(=O)=O.CC(C)=O.[Br:37]C(F)(F)C(Br)(F)F.[Li]C(C)(C)C.C([O-])(O)=O.[Na+]>C1COCC1>[Br:37][C:27]1[S:28][C:22]2[C:21](=[O:29])[N:20]([C:5]3[CH:6]=[CH:7][C:8]([O:9][Si:10]([CH:17]([CH3:19])[CH3:18])([CH:14]([CH3:15])[CH3:16])[CH:11]([CH3:12])[CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:25][CH2:24][C:23]=2[CH:26]=1

Participants

7

Reactant 5

HCID 313011,2-Dibromo-1,1,2,2-tetrafluoroethaneHCID 516892Sodium BicarbonateHCID 18522661Acetone cardiceHCID 689500376-(3-methoxy-4-triisopropylsilanyloxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-oneHCID 178418306HCID 178418306, compound2×

Product 1

HCID 689482602-Bromo-6-(3-methoxy-4-triisopropylsilanyloxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-oneYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Dissolve 6-(3-methoxy-4-triisopropylsilanyloxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one (5 g, 11.6 mmol) in THF (100 mL) in a three neck round bottom flask. Cool the solution in a dry ice/acetone bath. In one neck, set up a chilled (dry ice/acetone) addition funnel containing 1,2-dibromo-1,1,2,2-tetrafluoro-ethane (2.8 mL, 23.2 mmol) in 10 mL THF. Add t-BuLi (9.7 mL of 1.2 M solution in pentane, 11.6 mmol) quickly through one of the side necks allowing the solution to run down the inside of the flask. Within 30 sec of completion of the t-BuLi addition, open the addition funnel containing the electrophile. Stir 5-10 min, then pour into aqueous NaHCO3 (300 mL) and extract with EtOAc (2×300 mL). Wash the combined organic layers with brine (200 mL). Concentrate and purify via silica gel chromatography using a 0-25% gradient of EtOAc/hexanes to give 2.78 g (47%) of the desired product. MS/ES m/z (79Br) δ 10.0 [M+H]+; Rf=0.52 in 4:1 Hexanes:EtOAc.

Workup

  1. temperatureCool the solution in a dry ice/acetone bath
  2. temperaturea chilled
  3. additioncontaining the electrophile
  4. extractionextract with EtOAc (2×300 mL)
  5. washWash the combined organic layers with brine (200 mL)
  6. concentrationConcentrate
  7. custompurify via silica gel chromatography

Sources & evidence

ORD record
ord-f734b806d9294af4bc14c17f51afe304
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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