tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Was prepared according to method A with the following variation: n-BuLi (1.6 M in hexanes (1.93 mL, 4.82 mmol)) was added drop-wise to a solution of 2,6-dibromopyridine (1.06 g, 4.48 mmol) in dichloromethane (25 mL). The reaction was stirred −78° C. for 30 min. 9-Oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (300 mg, 1.12 mmol) in dichloromethane (5 mL) was added drop-wise and the mixture was stirred at −78° C. for 1 h. White solid. Mp. 161.3-162.8° C. Was prepared the mixture was stirred at −78° C. for 1 h

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Was prepared according to method A with the following variation: A solution of 5-bromo-2-chloroanisol (1.26 g, 5.7 mmol) in THF (7 mL) was added drop-wise to a solution of n-BuLi (1.6 M in hexanes (3.8 mL, 6.1 mmol)) at −78° C. and stirred for 30 min. A solution of 9-oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (475 mg, 1.78 mmol) in THF (7 mL) was added. The mixture was stirred for 1 h. White solid. Mp. 182-185° C. Was prepared The mixture was stirred for 1 h

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Was prepared according to method A with the following variation: A solution of 4-bromochlorobenzene (1.15 g, 5.98 mmol) in THF (5 mL) was added drop-wise to a solution of n-BuLi (1.6 M in hexanes (4 mL, 6.4 mmol)) at −78° C. and stirred for 30 min. A solution of 9-oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (500 mg, 1.87 mmol) in THF (5 mL) was added. The mixture was stirred for 1 h. White solid Mp. 104.2-107.1° C. Was prepared The mixture was stirred for 1 h

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Was prepared according to method A with the following variation: To a solution of 2-bromo-6-methoxynaphthalen in dry THF (30 mL) cooled to −40° C., tert-BuLi (1.5 M in pentane (5.55 mL)) was added drop-wise. The mixture was stirred for 1 h at −40° C. and then allowed to warm up to −10° C. 9-Oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (495 mg, 1.85 mmol) in dry THF (10 mL) was added drop-wise and stirred for 3 h at 0° C. Beige solid. Mp. 146.9-149.5° C. Was prepared to warm up to −10° C stirred for 3 h at 0° C

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Was prepared according to method A with the following variation: n-BuLi (1.6 M in hexanes (4 mL, 6.4 mmol)) was added drop-wise to a solution of benzothiophene (778 mg, 5.80 mL) in diethyl ether (10 mL). The reaction was warmed to reflux for 1 h and then cooled to −78° C. 9-Oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (500 mg, 1.87 mmol) in diethyl ether was added drop-wise and the mixture was stirred at −78° C. for 2 h. Mp. 107.3-110.2° C. Was prepared The reaction was warmed to reflux for 1 h

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-3,4-dichlorobenzene (1.35 g, 5.98 mmol) in THF (10 mL) was added drop-wise to a solution of n-BuLi (1.6 M in hexanes, 4 mL) at −78° C. The mixture was stirred for 40 min at −78° C. A solution of 9-oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (1 g, 3.74 mmol) in THF (10 mL) was added drop-wise and the mixture was stirred for 1 h at −78° C. The reaction was quenched with aqueous ammonium chloride and the aqueous layer was extracted twice with diethyl ether. The combined organic phase was washed with brine dried (sodium sulfate), filtered and evaporated to give 2.2 g of crude material. Precipitation in heptane and diethyl ether gave 547 mg of 9-(3,4-dichloro-phenyl)-9-hydroxy-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester. LC-ESI-HRMS of [M+H]+ shows 296.0983 Da. Calc. 296.09728 Da, dev. 3.4 ppm. the mixture was stirred for 1 h at −78° C The reaction was quenched with aqueous ammonium chloride the aqueous layer was extracted twice with diethyl ether The combined organic phase was washed with brine dried (sodium sulfate) filtered evaporated to give 2.2 g of crude material Precipitation in heptane

Conditions: temp:0.00; pressure:0.00; stir: