Sodium Carbonate → tert-butyl 4-(benzofuran-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1409858Notes

Reaction equation

HRID 1409858 reaction equation
Br[C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH:3]=1.CC1(C)C(C)(C)OB([C:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[O:4]1[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:2]([C:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]=2)=[CH:3]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 6405893-Bromo-1-benzofuranHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 70945173tert-butyl 4-(benzofuran-3-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 54.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of commercially available 3-bromobenzofurane (2.50 g, 12.7 mmol) and commercially available tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (4.32 g, 14.0 mmol) in 1,2-dimethoxyethane (85 ml) and 2M sodium carbonate solution (21.1 ml, 42.3 mmol) was purged with argon in an ultrasonic bath during 5 min. Then triphenylphosphine (666 mg, 2.54 mmol) and palladium(II)acetate (285 mg, 1.27 mmol) were added and the reaction mixture was allowed to stir at 85° C. for 17 h. The reaction mixture was cooled to room temperature, poured into water (30 ml) and extracted with diethyl ether (2×120 ml). The combined organic layers were washed with brine (60 ml), dried (MgSO4) and evaporated. The crude product (5.78 g) was further purified by flash chromatography on silica gel (heptane/ethyl acetate 4:1) to yield tert-butyl 4-(benzofuran-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate as a yellow oil (2.06 g, 54%), MS (ISP) m/z=300.2 [(M+H)+].

Workup

  1. customwas purged with argon in an ultrasonic bath during 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with diethyl ether (2×120 ml)
  4. washThe combined organic layers were washed with brine (60 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe crude product (5.78 g) was further purified by flash chromatography on silica gel (heptane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-bd92a29fef2d47759342fec326c175bc
Source dataset
uspto-grants-2014_12
Patent number
US08921397B2

Reaction notes

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