Tetrahydrofuran → (2-Amino-4-fluorophenyl)methanol

Temperature

23 °C

To a solution of 2-amino-4-fluorobenzoic acid (3.00 g, 19.3 mmol) and THF (40 mL) at 0° C. under argon, borane-THF complex (1M THF solution, 77.0 mmol) was added dropwise over 30 min. After complete addition, the reaction was warmed to 23° C. After 4 h, the reaction mixture was added slowly (5 min) to ethanol (77 mL). After 20 min, the reaction was concentrated in vacuo, diluted with sat'd NaHCO3 (100 mL), extracted with ethyl acetate (2×100 mL), washed with brine (1×100 mL), and dried (MgSO4). After concentration in vacuo, the residue was purified by passing through a silica gel pad (1:1 ethyl acetate:hexane). Concentration in vacuo afforded 2.02 g of 2-amino-4-fluorobenzyl alcohol as a yellow solid which was sufficiently pure to take on to the next step: 1H NMR (CDCl3) δ 4.54 (br s), 6.28-6.47 (m), 6.93-7.05 (m); 13C NMR (CDCl3) δ 62.7, 101.9 (J=24 Hz), 103.4 (J=21 Hz), 121.5, 130.1 (J=10 Hz), 149.1, 163 (J=360 Hz). MS (EI) 141 (M+), 124, 110. IR (neat) 3500-3000 cm−1.

1. additionAfter complete addition
2. waitAfter 20 min
3. concentrationthe reaction was concentrated in vacuo
4. additiondiluted with sat'd NaHCO3 (100 mL)
5. extractionextracted with ethyl acetate (2×100 mL)
6. washwashed with brine (1×100 mL)
7. dry with materialdried (MgSO4)
8. concentrationAfter concentration in vacuo
9. customthe residue was purified
10. concentrationConcentration in vacuo

ORD record

ord-99690f7c5bf84ac5b38aad69d42cbd5e

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06673784B1