tert-Butyl 3a-methyl-5-oxo-2,3,3a,4,5,6-hexahydro-1-carboxylate (CAS no.: ), which is also called as 1H-Indole-1-carboxylic acid, 2,3,3a,4,5,6-hexahydro-3a-methyl-5-oxo-, 1,1-dimethylethyl ester, could be produced through the following synthesis routes.

A. -2-ylcarbamic acid tert-butyl ester (CAS no ). In a 250-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar are placed 10 g (0.07 mol) of 2-furoyl chloride, 80 mL of tert-butyl alcohol, and 5.1 g (0.08 mol) of sodium azide. After the flask is stirred at 25°C for 20 hr under an atmosphere, it is placed behind a protective shield and the solution is heated at reflux for 15 hr under a constant flow of argon. The solvent is removed with a rotary evaporator at aspirator vacuum to provide a white solid that is purified by flash silica gel chromatography ( 10% ethyl acetate/hexane ) to give 10.8 g (81%) of furan-2-ylcarbamic acid tert-butyl ester as a white solid: mp 98-99°C.

B. 4-Bromo-2-methyl-1-butene (CAS no ). In a 500-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar, reflux condenser, and a dropping funnel are placed 20 g (0.23 mol) of 3-methyl-3-buten-1-ol, 160 mL of freshly distilled dichloromethane and 36 mL (0.24 mol) of triethylamine. The reaction mixture is cooled to -5°C and 14.4 g (0.24 mol) of freshly distilled methanesulfonyl chloride is added dropwise from the dropping funnel. After the reaction mixture is stirred at 0°C for an additional 2 hr, it is quenched with 80 mL of water and the aqueous phase is extracted three times with 40-mL portions of dichloromethane . The combined organic phase is dried over magnesium sulfate and the solvent is removed with a rotary evaporator at aspirator vacuum. The crude yellow oil is taken up in 25 mL of dry acetone and added dropwise from a dropping funnel to a slurry of 60 g (0.68 mol) of lithium bromide in 115 mL of dry acetone in a 250-mL round-bottomed flask fitted with the dropping funnel and a reflux condenser. The solution is slowly warmed to 35°C and is stirred at this temperature for 18 hr, at which time the reaction is quenched with 120 mL of water. The aqueous phase is extracted three times with 40-mL portions of ether. The combined organic phase is dried over magnesium sulfate and the solvent is removed with a rotary evaporator at aspirator vacuum. The resulting oil is distilled at aspirator pressure to provide 17.7 g (51%) of 4-bromo-2-methyl-1-butene as a colorless oil: bp 41-42°C at 34-39 torr.

C. tert-Butyl N-(3-methyl-3-butenyl)-N-(2-furyl)carbamate (CAS no ). In a flame-dried, 500-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar and reflux condenser are placed 4.0 g (21.8 mmol) of furan-2-ylcarbamic acid tert-butyl ester and 150 mL of toluene under an argon atmosphere. To this solution are added 3.1 g (76.4 mmol) of freshly ground powdered sodium hydroxide , 6.04 g (43.7 mmol) of potassium carbonate , and 1.48 g (4.4 mmol) of tetrabutylammonium hydrogen sulfate. The solution is heated at 80°C for 25 min with vigorous stirring and then 3.9 g (26.2 mmol) of freshly distilled 4-bromo-2-methyl-1-butene is added as a solution in 10 mL of toluene over a 30-min period. After being heated at 80°C for 30 min, the solution is charged with an additional 0.98 g (6.6 mmol) of 4-bromo-2-methyl-1-butene . The mixture is heated at 80°C for an additional 1 hr. After the reaction is cooled to room temperature, it is quenched by the addition of 200 mL of water and the aqueous phase is extracted three times with 100-mL portions of dichloromethane . The combined organic phase is dried over magnesium sulfate and the solvent is removed with a rotary evaporator at aspirator vacuum. The crude residue is purified by silica gel chromatography ( 10% ethyl acetate-hexane ) to give 5.0 g (91%) of tert-butyl N-(3-methyl-3-butenyl)-N-(2-furyl)carbamate as a colorless oil.

D. tert-Butyl 3a-methyl-5-oxo-2,3,3a,4,5,6-hexahydroindole-1-carboxylate (CAS no ). Into an oven-dried, 35-mL heavy-wall, high pressure tube equipped with a magnetic stirring bar and rubber septum are placed 3.7 g (14.7 mmol) of tert-butyl N-(3-methyl-3-butenyl)-N-(2-furyl)carbamate and 20 mL of toluene under an argon atmosphere. Argon is vigorously bubbled through the solution for 30 min at which time the septum is replaced with a threaded plunger valve equipped with an O-ring seal. The vessel is placed behind a protective shield and immersed into a preheated oil bath at 160°C for 14 hr. After the solution is cooled to room temperature, solvent is removed with a rotary evaporator at aspirator vacuum and the crude residue is purified by silica gel chromatography ( 40% ethyl acetate-hexane ) to give 2.8 g (70-75%) of tert-butyl 3a-methyl-5-oxo-2,3,3a,4,5,6-hexahydroindole-1-carboxylate as a white solid: mp 112-113°C.