Sodium Hydroxide → 2-Fluoro-6-(2-pyrimidinyl)benzoic acid

HRID 1524947Notes

Reaction equation

HRID 1524947 reaction equation
C[O:2][C:3](=[O:17])[C:4]1[C:9]([C:10]2[N:15]=[CH:14][CH:13]=[CH:12][N:11]=2)=[CH:8][CH:7]=[CH:6][C:5]=1[F:16].[OH-].[Na+]>>[F:16][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([C:10]2[N:11]=[CH:12][CH:13]=[CH:14][N:15]=2)[C:4]=1[C:3]([OH:17])=[O:2]

Participants

3

Reactant 2

HCID 14798Sodium HydroxideHCID 67086836Methyl 2-fluoro-6-(pyrimidin-2-yl)benzoate

Product 1

HCID 670866032-Fluoro-6-(2-pyrimidinyl)benzoic acidYield 88%

Conditions

Temperature
72 °C

Procedure

To a solution of 2-fluoro-6-pyrimidin-2-yl-benzoic acid methyl ester (1.36 g, 5.85 mmol) in 2-methyl-THF (20 mL) was added sodium hydroxide (2 M in water, 9.3 mL, 18.6 mmol). The mixture was heated to 72° C. and stirred for 9 h. The layers were separated and the aqueous layer acified to pH 2 by dropwise addition of 50% HCl(aq) (3.1 mL). The resulting solids were stirred for 1 h, filtered, washed with water, MTBE, and heptanes, and then dried to provide the desired product as a white solid (1.12 g, 88% yield). 1H NMR (400 MHz, CD3OD): 8.83 (d, J=4.9 Hz, 2H), 8.03 (dd, J=7.9, 0.8 Hz, 1H), 7.59 (td, J=8.1, 5.6 Hz, 1H), 7.40 (t, J=4.9 Hz, 1H), 7.34 (ddd, J=9.4, 8.4, 1.0 Hz, 1H).

Workup

  1. customThe layers were separated
  2. additionthe aqueous layer acified to pH 2 by dropwise addition of 50% HCl(aq) (3.1 mL)
  3. stirringThe resulting solids were stirred for 1 h
  4. filtrationfiltered
  5. washwashed with water, MTBE, and heptanes
  6. customdried

Sources & evidence

ORD record
ord-ebd0adb682ab419d8012c01bde8256a1
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

Loading…