Water → tert-butyl N-(4-fluoropyridin-2-yl)carbamate

HRID 1894973Notes

Reaction equation

HRID 1894973 reaction equation
Cl[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][N:3]=1.[C:9](=[O:16])([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[NH2:10].[OH-].[Na+].O>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[F:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:10][C:9](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 77922tert-Butyl carbamateHCID 27827922-Chloro-4-fluoropyridine

Product 1

HCID 51354888tert-butyl N-(4-fluoropyridin-2-yl)carbamateYield 79.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Palladium(II) acetate (341 mg, 1.52 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.76 g, 3.04 mmol) were added to a 3-necked round bottomed flask, and the flask was purged three times with argon. Degassed 1,4-dioxane (240 mL) was added and the mixture was stirred and degassed again with argon. To this solution was added a solution of 2-chloro-4-fluoropyridine (20 g, 152 mmol) in degassed 1,4-dioxane (120 mL), tert-butyl carbamate (19.6 g, 167 mmol), NaOH (8.88 g, 222 mmol) and degassed water (4 mL, 222 mmol). The resulting mixture was stirred at 100° C. under argon. After 1.5 h, the reaction mixture was cooled to room temperature and filtered through a pad of Celite®. The pad was washed well with dioxane and the filtrate was concentrated under reduced pressure to dryness. The resulting solid was recrystallized from 2-propanol (˜250 mL) to give tert-butyl (4-fluoropyridin-2-yl)carbamate as a pale yellow crystalline solid (25.65 g, 79.5% yield). LC-MS: (FA) ES+213; 1H NMR (400 MHz, d6-DMSO) δ ppm 10.1 (s, 1H), 8.26 (dd, J=9.5, 5.6 Hz, 1H), 7.60 (dd, J=12.3, 2.3 Hz, 1H), 6.95 (ddd, J=8.3, 5.6, 2.3 Hz, 1H), 1.47 (s, 9H).

Workup

  1. customthe flask was purged three times with argon
  2. additionDegassed 1,4-dioxane (240 mL) was added
  3. customdegassed again with argon
  4. stirringThe resulting mixture was stirred at 100° C. under argon
  5. filtrationfiltered through a pad of Celite®
  6. washThe pad was washed well with dioxane
  7. concentrationthe filtrate was concentrated under reduced pressure to dryness
  8. customThe resulting solid was recrystallized from 2-propanol (˜250 mL)

Sources & evidence

ORD record
ord-72267f5b6fbd463ab16d4c7ce2165e70
Source dataset
uspto-grants-2013_08
Patent number
US08513421B2

Reaction notes

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