Diisopropylamine → HCID 747438, compound

Temperature

15 °C

A solution of diisopropyl amine (13 mL, 100 mmol) and tetramethylethylene diamine (15 mL, 100 mmol) in THF (150 mL) was cooled in dry ice-acetone bath under argon atmosphere. A 2.5N solution of n-butyl lithium in hexane (40 mL, 100 mmol) was added over 30 minutes and EtOAc (10 mL, 108 mmol) was added and solution stirred for additional 30 minutes. A solution of N-BOC methyl indole-3-carboxylate (IIIa) (6.875 g, 25 mmol), in THF (50 mL) was added rapidly and the reaction mixture was stirred at −78° C. for 1 h and then at −15° C. for an additional 1 h. Reaction mixture was allowed to warm to 15° C., and the reaction was quenched with glacial acetic acid (10 mL). Ethyl acetate (250 mL) was added and the organic layer was successively washed with 1N citric acid solution (2×150 mL), saturated brine (2×100 mL), the organic layer was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The crude product was purified was purified by flash chromatography over silica gel and 1:1 ethyl acetate and hexane were used as eluent to provide the desired compound (Va) (1.2 g) and its N-BOC derivative (Vb) (1.2 g) in a combined yield of 30%.

1. stirringthe reaction mixture was stirred at −78° C. for 1 h
2. waitat −15° C. for an additional 1 h
3. customReaction mixture
4. customthe reaction was quenched with glacial acetic acid (10 mL)
5. additionEthyl acetate (250 mL) was added
6. washthe organic layer was successively washed with 1N citric acid solution (2×150 mL), saturated brine (2×100 mL)
7. dry with materialthe organic layer was dried over anhydrous sodium sulphate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified
11. customwas purified by flash chromatography over silica gel and 1:1 ethyl acetate and hexane

ORD record

ord-e6343fd614c34c0a820a3000e53b8d85

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06455525B1