Sodium Carbonate → 4-Benzo[1,3]dioxol-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 1909355Notes

Reaction equation

HRID 1909355 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=2)O1.Br[C:24]1[C:32]2[O:31][CH2:30][O:29][C:28]=2[CH:27]=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>COCCOC.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:18]([O:17][C:15]([N:12]1[CH2:11][CH:10]=[C:9]([C:24]2[C:32]3[O:31][CH2:30][O:29][C:28]=3[CH:27]=[CH:26][CH:25]=2)[CH2:14][CH2:13]1)=[O:16])([CH3:19])([CH3:20])[CH3:21]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27761894-Bromo-1,3-benzodioxoleHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 706568674-Benzo[1,3]dioxol-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterYield 80.9%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
85 °C

Procedure

Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (1.62 g, 5.22 mmol) was added to a solution of 4-bromobenzo[d][1,3]dioxole (1 g, 4.97 mmol) in 1,2-Dimethoxyethane (45.0 ml) and Na2CO3 2M (8.28 ml, 16.6 mmol). The resulting suspension was degassed using a stream of argon in an ultrasonic bath during 5 min. Then triphenylphosphine (261 mg, 995 μmol) and palladium (II) acetate (112 mg, 497 μmol) was added and the reaction mixture was stirred over night at 85° C. The reaction was cooled to rt, diluted with 40 mL of water and the mixture extracted with ethyl acetate (3×50 mL). The organic layers were dried over MgSO4 and concentrated under vacuum. The crude material was purified by flash chromatography (silica gel, 50 g, 0% to 50% EtOAc in heptane) to yield 4-Benzo[1,3]dioxol-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as a yellowish liquid (1.22 g, 80.8%). MS (ISP) m/z=304.4 [(M+H)+].

Workup

  1. customThe resulting suspension was degassed
  2. customduring 5 min
  3. temperatureThe reaction was cooled to rt
  4. extractionthe mixture extracted with ethyl acetate (3×50 mL)
  5. dry with materialThe organic layers were dried over MgSO4
  6. concentrationconcentrated under vacuum
  7. customThe crude material was purified by flash chromatography (silica gel, 50 g, 0% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-e92bcd3645914b918d658d39b3b14e25
Source dataset
uspto-grants-2013_12
Patent number
US08598357B2

Reaction notes

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