tert-Butyl acetate → Tert-butyl 3-[4,6-dibromo-2-(2-chloro-4-fluorophenyl)pyridin-3-yl]propanoate

HRID 394177Notes

Reaction equation

HRID 394177 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])[CH3:12].[Br:19][C:20]1[CH:25]=[C:24]([Br:26])[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[Cl:34])[C:21]=1[CH2:35]Br>C1COCC1>[Br:19][C:20]1[CH:25]=[C:24]([Br:26])[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[Cl:34])[C:21]=1[CH2:35][CH2:12][C:11]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 2733832Lithium HexamethyldisilazideHCID 226479624,6-Dibromo-3-(bromomethyl)-2-(2-chloro-4-fluorophenyl)pyridine

Product 1

HCID 22647943Tert-butyl 3-[4,6-dibromo-2-(2-chloro-4-fluorophenyl)pyridin-3-yl]propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a 1M solution of lithium bis(trimethlsilyl)amide (10.5 mL) at −78° C. was added tert-butyl acetate (1.77 mL, 13.2 mmol) dropwise. To this mixture a solution of 4,6-dibromo-3-(bromomethyl)-2-(2-chloro-4-fluorophenyl)pyridine (4.02 g, 8.77 mmol) (COMPOUND PS) in 9.2 mL of THF was added dropwise over 20 min. After stirring for 30 min at −78° C., the reaction mixture was quenched by the dropwise addition of 3 mL of methanol, then warmed up to rt and partitioned between 30 mL each of saturated aqueous NaHCO3 and ethyl acetate. The aqueous phase was extracted with 2×20 mL of ethyl acetate. The combined organic layers were washed with brine (20 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was triturated with warm Et2O. The mother liquor was purified by flash chromatography on a Biotage 40M column eluting with 97:3 hexanes-ethyl acetate. The two batches were combined to give the tert-butyl 3-[4,6-dibromo-2-(2-chloro-4-fluorophenyl)pyridin-3-yl]propanoate. Mass spectrum (ESI) 492.4 (M+1).

Workup

  1. customthe reaction mixture was quenched by the dropwise addition of 3 mL of methanol
  2. temperaturewarmed up to rt
  3. custompartitioned between 30 mL each of saturated aqueous NaHCO3 and ethyl acetate
  4. extractionThe aqueous phase was extracted with 2×20 mL of ethyl acetate
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was triturated with warm Et2O
  9. customThe mother liquor was purified by flash chromatography on a Biotage 40M column
  10. washeluting with 97:3 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-6e472e3362fb47dda879cf340a2528c0
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

Loading…