Sodium Carbonate → methyl 2-(tert-butoxy)-2-[3-(3,4-dihydro-2H-1-benzopyran-6-yl)imidazo[1,2-a]pyridin-2-yl]acetate

HRID 591044Notes

Reaction equation

HRID 591044 reaction equation
Br[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[CH:11]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:12]([O:14][CH3:15])=[O:13].C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:35]2[CH:36]=[C:37]3[C:42](=[CH:43][CH:44]=2)[O:41][CH2:40][CH2:39][CH2:38]3)O1>C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].O.C(O)C>[C:17]([O:16][CH:11]([C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]2[C:2]=1[C:35]1[CH:44]=[CH:43][C:42]2[O:41][CH2:40][CH2:39][CH2:38][C:37]=2[CH:36]=1)[C:12]([O:14][CH3:15])=[O:13])([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 438110342-(3,4-dihydro-2H-1-benzopyran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 70819495HCID 70819495, compound

Product 1

HCID 86717841methyl 2-(tert-butoxy)-2-[3-(3,4-dihydro-2H-1-benzopyran-6-yl)imidazo[1,2-a]pyridin-2-yl]acetateYield 45%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of methyl 2-{3-bromoimidazo[1,2-a]pyridin-2-yl}-2-(tert-butoxy)acetate (25d) (60 mg, 0.175 mmol), sodium carbonate (75 mg, 0.70 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (82 mg, 0.32 mmol) and palladium tetrakis(triphenylphosphine) (20 mg, 0.018 mmol) in a mixture of toluene (1.1 mL), water (0.55 mL) and ethanol (0.48 mL) was heated at 85° C. overnight. After cooling to room temperature, the mixture was poured into water (10 mL). The aqueous layer was extracted with ethyl acetate (2×5 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 50/50). The residue containing target compound was dissolved in ethyl acetate (5 mL) and washed with 1M hydrochloric acid aqueous solution (5 mL). The acidic layer was basified with a saturated solution of sodium hydrogenocarbonate and extracted with ethyl acetate (2×5 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to provide the desired product (25e) (31 mg, 0.078 mmol, 45%).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×5 mL)
  3. washThe organic layer was washed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 50/50)
  7. additionThe residue containing target compound
  8. dissolutionwas dissolved in ethyl acetate (5 mL)
  9. washwashed with 1M hydrochloric acid aqueous solution (5 mL)
  10. extractionextracted with ethyl acetate (2×5 mL)
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-96f41f890137476a96ce118cb237731b
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

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