Sodium Carbonate → HCID 67155323, compound

HRID 536410Notes

Reaction equation

HRID 536410 reaction equation
[F:1][C:2]1[CH:8]=[C:7](B2OC(C)(C)C(C)(C)O2)[C:6]([CH3:18])=[CH:5][C:3]=1[NH2:4].[CH3:19][CH:20]1[CH:25]=[C:24](OS(C(F)(F)F)(=O)=O)[CH2:23][CH2:22][N:21]1[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O.[Pd].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>[NH2:4][C:3]1[C:2]([F:1])=[CH:8][C:7]([C:24]2[CH2:25][CH:20]([CH3:19])[N:21]([C:34]([O:36][C:37]([CH3:38])([CH3:40])[CH3:39])=[O:35])[CH2:22][CH:23]=2)=[C:6]([CH3:18])[CH:5]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 22495589HCID 22495589, compoundHCID 59232206HCID 59232206, compound

Product 1

HCID 67155323HCID 67155323, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 2-fluoro-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (587 mg, 2.33 mmol), tert-butyl 2-methyl-4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (968 mg, 2.80 mmol) and sodium carbonate (1.73 g, 16.35 mmol) in DMF/H2O (20/5 mL) was added tetrakis(triphenylphosphine) palladium (0) (135 mg, 5% mmol). The reaction tube was sealed, the mixture was purged with N2 for 3 min and then heated at 100° C. under N2 for 8 h. The reaction was cooled to room temperature and poured into saturated aqueous ammonia chloride solution. The crude reaction mixture was extracted with ethyl acetate (3×15 mL). The organic extracts were combined, washed with brine and concentrated. The crude product was purified with silica chromatography (50% ethyl acetate in hexanes) to afford tert-butyl 4-(4-amino-5-fluoro-2-methylphenyl)-6-methyl-5,6-dihydropyridine-1(2H)-carboxylate as a yellow oil. The obtained oil was dissolved in methanol (20 mL). To the solution was added Pd/C (10%). The reaction mixture was degassed and purged with H2 for several times and stirred vigorously under 1 atm. H2 overnight. The mixture was filtered and the filtrate concentrated to afford tert-butyl 4-(4-amino-5-fluoro-2-methylphenyl)-2-methylpiperidine-1-carboxylate as a white solid. ESMS m/z 267 (M−56+H+).

Workup

  1. customThe reaction tube was sealed
  2. customthe mixture was purged with N2 for 3 min
  3. temperatureThe reaction was cooled to room temperature
  4. additionpoured into saturated aqueous ammonia chloride solution
  5. customThe crude reaction mixture
  6. extractionwas extracted with ethyl acetate (3×15 mL)
  7. washwashed with brine
  8. concentrationconcentrated
  9. customThe crude product was purified with silica chromatography (50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3c7c898c7d9c4c3abaeee1ad3412fbb4
Source dataset
uspto-grants-2014_10
Patent number
US08859574B2

Reaction notes

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