4-(HYDROXYMETHYL)PHENYLACETIC ACID synthesis

Yield:73401-74-8 71.9%

Reaction Conditions:

with sodium hydroxide in water at 18 - 25;Large scale;

Steps:

1 2-(4-(Hydroxymethyl)phenyl)acetic acid (C)

2-(4-(Hydroxymethyl)phenyl)acetic acid (C)
To a solution of NaOH (1.61 kg, 40.2 mol, 4 eq) in water (90 L) was added B (2.3 kg, 10.0 mol, 1 eq) and the resulting mixture was stirred at RT overnight. TLC analysis indicated consumption of B.
The reaction mixture was then carefully acidified with concentrated H₂SO₄ (1.0 L) to pH?2.
Then, solid NaCl (25 kg) was added to the mixture followed by extraction with EtOAc (33 L*3).
The combined organic phase was washed with brine, dried over Na₂SO₄, and concentrated until a significant amount of solid precipitated.
The resulting suspension was kept at ?4-6° C. overnight to allow for further crystallization.
The solid product was then collected by filtration.
The filter cake was washed with petroleum ether (2 L*2) to yield the title compound (1.2 kg, yield: 71.9%). HPLC purity: 97.8% (220 nm); ¹H NMR (300 MHz, DMSO-d₆) δ 12.27 (s, 1H), 7.26-7.12 (m, 4H), 5.14 (s, 1H), 4.47 (s, 2H), 3.53 (s, 2H).

References:

US9643927,2017,B1 Location in patent:Page/Page column 33;34