Acetyl chloride → N-[2-(Hydroxymethyl)-1H-indol-5-yl]acetamide

To a solution of 14 (200 mg, 1.25 mmol), dimethylaminopyridine (20 mg) and triethylamine (0.94 mL) in THF cooled to 0° C. was added a solution of acetyl chloride (0.30 mL, 4.16 mmol) in THF (5 mL) dropwise. The reaction mixture was allowed to warm up to room temperature and stirred for 3 h. THF was removed in vacuo and ethyl acetate (40 mL) was added. The solution was washed with water (20 mL×2). The solution was dried using sodium sulfate and solvent was removed in vacuo. The residue was dissolved in methanol (5 mL) and 3N NaOH solution(1 mL) was added. The reacted was allowed to proceed overnight. The reaction mixture was evaporated and water (10 mL) was added. The product was extracted with ethyl acetate (30 mL×3) and the solvent was removed in vacuo. The product was crystallized in acetate and washed with ether. 128 mg (50% yield) of grew powder 15 was obtained. mp: 161° C. 1H NMR (DMSO-d6, ppm): 10.84 (s, 1 H, NH), 9.62 (s, 1 H, NH), 7.75 (d, 1 H, J=2.1 Hz, Ar--H), 7.22-7.10 (m, 2 H, Ar--H), 6.20 (s, 1 H, Ar--H), 6.43-6.40 (dd, 1 H, J=2.4, 8.5 Hz, Ar--H), 5 5.18-5.15 (t, 1 H, J=5.5 Hz, OH), 4.57-4.56 (d, 2 H, J=5.4 Hz, CH2OH), 2.01 (s, 3 H, CH3), Anal. (C11H12N2O2), C, H, N.

1. customTHF was removed in vacuo and ethyl acetate (40 mL)
2. additionwas added
3. washThe solution was washed with water (20 mL×2)
4. customThe solution was dried
5. customwas removed in vacuo
6. dissolutionThe residue was dissolved in methanol (5 mL)
7. addition3N NaOH solution(1 mL) was added
8. waitto proceed overnight
9. customThe reaction mixture was evaporated
10. additionwater (10 mL) was added
11. extractionThe product was extracted with ethyl acetate (30 mL×3)
12. customthe solvent was removed in vacuo
13. customThe product was crystallized in acetate
14. washwashed with ether

ORD record

ord-2827dae181f34991a73b5a0c2a61c49e

Source dataset

uspto-grants-1998_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05843937