Benzoyl chloride → N-(3-fluoropyridin-4-yl)benzamide

HRID 1257563

Reaction equation

HRID 1257563 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[NH2:8].C(N(CC)CC)C.[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O1CCCC1>[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[NH:8][C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 8171224-Amino-3-fluoropyridine

Product 1

HCID 67323663N-(3-fluoropyridin-4-yl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-fluoropyridin-4-amine (2.20 kg, 19.6 mol) in anhydrous tetrahydrofuran (25 L) was cooled to −5° C. and flushed with nitrogen. This solution was charged with triethylamine (3.99 kg/5.5 L, 39.4 mol). Benzoylchloride (3.173 kg/2.62 l, 22.57 mol) was added drop-wise via an addition funnel over two hours while the internal temperature was maintained between −5° C. to 5° C. and the reaction mixture was left to stand for an additional two hours. The reaction mixture was then filtered and washed with dry tetrahydrofuran (5×20 L). The tetrahydrofuran solution was concentrated under vacuum to give crude product which was recrystallized from ethyl acetate and hexane, filtered and dried to afford N-(3-fluoro-pyridin-4-yl)-benzamide, 3.90 kg, (92%). 1H NMR (400 MHz, CDCl3): δ 8.51 (1H, t, J=5.46 Hz), 8.45 (1H, d, J=2.34 Hz), 8.39 (1H, d, J=5.46 Hz), 8.30 (1H, s), 7.89 (2H, d, J=8.20 Hz), 7.62 (1H, t, J=7.03 Hz), 7.53 (2H, t, J=7.81 Hz).

Workup

  1. customflushed with nitrogen
  2. temperaturewas maintained between −5° C. to 5° C.
  3. waitthe reaction mixture was left
  4. filtrationThe reaction mixture was then filtered
  5. washwashed with dry tetrahydrofuran (5×20 L)
  6. concentrationThe tetrahydrofuran solution was concentrated under vacuum
  7. customto give crude product which
  8. customwas recrystallized from ethyl acetate and hexane
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-6d825bb517b0472cb14395dcb7176b25
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Linked notes

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