Water → N-(2-(benzyloxy)phenyl)-3-fluoroisonicotinamide

HRID 1946573Notes

Reaction equation

HRID 1946573 reaction equation
[F:1][C:2]1[CH:10]=[N:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH2:11]([O:18][C:19]1[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=1[NH2:21])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.O>CN(C=O)C>[CH2:11]([O:18][C:19]1[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=1[NH:21][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][N:9]=[CH:10][C:2]=1[F:1])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2405482-BenzyloxyanilineHCID 3453613-Fluoropyridine-4-carboxylic acid

Product 1

HCID 59783597N-(2-(benzyloxy)phenyl)-3-fluoroisonicotinamideYield 97.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-fluoroisonicotinic acid (2.20 g, 15.6 mmol), 2-(benzyloxy)aniline (2.84 g, 14.2 mmol) and BOP (6.94 g, 15.6 mmol) in DMF (20.0 mL) was added TEA (4.4 mL, 31.2 mmol). The reaction mixture was stirred at room temperature for 20 min and poured into water. The aqueous layer was extracted with ethyl acetate (2×). The combined organic extracts were washed with water and brine, dried over sodium sulfate and concentrated in vacuo to a quarter volume. The resulting solid was found to be the desired compound. The filtrate was concentrated in vacuo to dryness. The residue was triturated in 30% ethyl acetate in hexanes and the 2 solids were combined to afford compound 24 (4.45 g, 97%) as a white solid. LRMS (ESI): (calc) 322.11 (found) 323.2 (MH)+.

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo to a quarter volume
  5. concentrationThe filtrate was concentrated in vacuo to dryness
  6. customThe residue was triturated in 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-70eb2514cab04488bdb2a62567676043
Source dataset
uspto-grants-2013_03
Patent number
US08399452B2

Reaction notes

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