Carbon Dioxide → 5-Bromo-2,3-difluoro-4-(trimethylsilyl)benzoic acid

HRID 1879630Notes

Reaction equation

HRID 1879630 reaction equation
[Li]CCCC.CC1(C)CCCC(C)(C)N1.[Br:16][C:17]1[C:22]([Si:23]([CH3:26])([CH3:25])[CH3:24])=[C:21]([F:27])[C:20]([F:28])=[CH:19][CH:18]=1.[C:29](=[O:31])=[O:30]>C1COCC1.O>[Br:16][C:17]1[C:22]([Si:23]([CH3:24])([CH3:25])[CH3:26])=[C:21]([F:27])[C:20]([F:28])=[C:19]([CH:18]=1)[C:29]([OH:31])=[O:30]

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 130352,2,6,6-TetramethylpiperidineHCID 23070109(6-Bromo-2,3-difluorophenyl)trimethylsilaneHCID 178418339Butyllithium

Product 1

HCID 585380595-Bromo-2,3-difluoro-4-(trimethylsilyl)benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of n-BuLi (2.0 M in hexanes, 11.1 mL, 22.2 mmol) in anhydrous THF (17 mL) at −78° C. was added drop wise 2,2,6,6-tetramethylpiperidine (3.26 g, 22.1 mmol). After being stirred for 15 minutes, a solution of the product from step A (5.86 g, 22.1 mmol) in THF (20 mL) was added. The reaction mixture was stirred at −78° C. for 2 hours, then dry ice (100 g) was added. The mixture was allowed to stand at room temperature overnight, then it was diluted with water and extracted with EtOAc. The combined organics were dried over MgSO4, filtered, then concentrated to afford the title compound. The material was used directly in the next step without further purification. 1H NMR (500 MHz, CDCl3): δ 7.70 (d, J=4.4 Hz, 1H); 0.44 (s, 9H).

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 2 hours
  2. waitto stand at room temperature overnight
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a6c8e712035e4145a4b7fd1cc77e887a
Source dataset
uspto-grants-2012_11
Patent number
US08318667B2

Reaction notes

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