Toluene → tert-butyl 5-(hydroxymethyl)-1H-indole-1-carboxylate

To a solution of N-tert-butoxycarbonylindole-5-carboxylic acid methyl ester (23.6 g, 85.7 mmol) in dry tetrahydrofuran (225 mL) at −78° C. was added 1.5 M DIBALH in toluene (171 mL, 257 mmol). After 2 h, the reaction mixture was quenched by the slow addition of methanol (45 mL), water (60 mL), and saturated aqueous NH4Cl (30 mL). The cold bath was removed and after stirring for an additional 1 h, the reaction mixture was filtered over Celite. The Celite cake was washed with tetrahydrofuran and the filtrate was concentrated to remove the more volatile tetrahydrofuran. The biphasic mixture was extracted with ethyl acetate. The combined organic layers were washed with water and the aqueous layer back extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated to afford N-tert-butoxycarbonylindol-5-yl methanol (21.2 g).

1. customthe reaction mixture was quenched by the slow addition of methanol (45 mL), water (60 mL), and saturated aqueous NH4Cl (30 mL)
2. customThe cold bath was removed
3. filtrationthe reaction mixture was filtered over Celite
4. washThe Celite cake was washed with tetrahydrofuran
5. concentrationthe filtrate was concentrated
6. customto remove the more volatile tetrahydrofuran
7. extractionThe biphasic mixture was extracted with ethyl acetate
8. washThe combined organic layers were washed with water
9. extractionthe aqueous layer back extracted with ethyl acetate
10. washThe combined organic layers were washed with brine
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated

ORD record

ord-b11474a792c74de8bc0035b1ec928068

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06492394B1