Benzenepropanoyl chloride → HCID 12112436, compound

To a solution of 2-amino-4-fluorobenzyl alcohol from Step 1 (2.00 g, 14.17 mmol) and methylene chloride (45 mL), was added N,N,-diisopropylethylamine (3.70 g, 28.34 mmol) followed by hydrocinnamoyl chloride (4.78 g, 28.34 mmol) dropwise over 15 min under an argon atmosphere at 23° C. After 16 h, the reaction was diluted with methylene chloride (100 mL), washed with KHSO4 (1 N, 1×80 mL), sat'd NaHCO3 (1×80 mL), brine (1×80 mL) and dried (MgSO4). After concentration in vacuo, the crude residue was dissolved in methanol (14 mL) and NaOH (1.5 N, 14 mL) was added at 23° C. under argon. After 2 h at 23° C., the reaction was concentrated in vacuo, diluted with ether (150 mL), washed with brine (100 mL), and dried (MgSO4). After concentration in vacuo, the residue was purified by flash chromatography (ethyl acetate:hexane 1:3) to afford N-[5-fluoro-2-hydroxymethylphenyl]benzenepropanamide (3.40 g, 87.8%) as an oil: 1H NMR (CDCl3) δ2.65 (t, J=7 Hz), 3.05 (t, J=7 Hz), 4.48 (s), 6.68-6.74 (m), 7.00-7.34 (m), 7.83-7.91 (m) 8.72 (br s). MS (EI) 273, 255, 212. IR (neat) 3500-3150, 1667 cm−1. Anal. Calc'd. for C16H16NO2F: C, 70.31; H, 5.90; N, 5.13. Found: C, 70.26; H, 6.11; N, 5.03.

1. washwashed with KHSO4 (1 N, 1×80 mL), sat'd NaHCO3 (1×80 mL), brine (1×80 mL)
2. dry with materialdried (MgSO4)
3. concentrationAfter concentration in vacuo
4. dissolutionthe crude residue was dissolved in methanol (14 mL)
5. additionNaOH (1.5 N, 14 mL) was added at 23° C. under argon
6. waitAfter 2 h at 23° C.
7. concentrationthe reaction was concentrated in vacuo
8. additiondiluted with ether (150 mL)
9. washwashed with brine (100 mL)
10. dry with materialdried (MgSO4)
11. concentrationAfter concentration in vacuo
12. customthe residue was purified by flash chromatography (ethyl acetate:hexane 1:3)

ORD record

ord-1ed7dc8b77644a1aaa5b3345d4a316d2

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06673788B2