1,3-dibromo-2-ethylbenzene

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

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

Procedure: A three necked round-bottom flask was purged with argon and then filled with dry THF (1.2 I), 1,3-dibromo benzene (121 g, 0.514 mol) and ethyl iodide (95.4 g, 0.611 mol). The mixture was cooled to −78° C. and LDA (64.2 g, 0.697 mol) (2 M in THF/n-heptane/ethylbenzene) was added slowly in a way that the temperature didn't rise above −65° C. After stirring for 2.75 h the reaction was poured onto 11 sat. aq NH4Cl solution and stirred vigorously for 20 min. Extraction with DCM (twice) yielded a colorless oil (167 g) which was used in the next step without further purification A three necked round-bottom flask was purged with argon rise above −65° C stirred vigorously for 20 min Extraction with DCM (twice)

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

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

Procedure: A three necked round-bottom flask was purged with argon and then filled with dry THF (1.2 I), 1,3-dibromo benzene (121 g, 0.514 mol) and ethyl iodide (95.4 g, 0.611 mol). The mixture was cooled to −78° C. and LDA (64.2 g, 0.697 mol) (2 M in THF/n-heptane/ethylbenzene) was added slowly in a way that the temperature didn't rise above −65° C. After stirring for 2.75 h the reaction was poured onto 11 sat. aq NH4Cl solution and stirred vigorously for 20 min. Extraction with DCM (twice) yielded a colorless oil (167 g) which was used in the next step without further purification A three necked round-bottom flask was purged with argon rise above −65° C stirred vigorously for 20 min Extraction with DCM (twice)

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

Procedure: A three necked round-bottom flask was purged with argon and then filled with dry THF (1.2 I), 1,3-dibromo benzene (121 g, 0.514 mol) and ethyl iodide (95.4 g, 0.611 mol). The mixture was cooled to −78° C. and LDA (64.2 g, 0.697 mol) (2 M in THF/n-heptane/ethylbenzene) was added slowly in a way that the temperature didn't rise above −65° C. After stirring for 2.75 h the reaction was poured onto 11 sat. aq NH4Cl solution and stirred vigorously for 20 min. Extraction with DCM (twice) yielded a colorless oil (167 g) which was used in the next step without further purification A three necked round-bottom flask was purged with argon rise above −65° C stirred vigorously for 20 min Extraction with DCM (twice)

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a three litre neck round flask charged with 19.30 g of diisopropylamine and 110 mL of THF was added 76 mL of n-BuLi in hexane (2.5 M) in dropwise at −70° C. After addition was finished, the resulting mixture was stirred at the same temp. for 10 min. In another 500 mL three neck round flask, 25 g of 1,3-dibromobenzene and 49.6 g of ethyl iodide was mixed well and cooled to −70° C. The freshly prepared LDA was introduced dropwise to above mixture below −65° C. After the addition was finished, the resulting mixture was stirred for 4 h at the same temp. GCMS showed that the desired product was formed. The reaction was warmed to 0° C. in 30 mins. To the reaction mixture was added 100 mL of sat. ammonium chloride solution to quench the reaction. After addition After the addition the resulting mixture was stirred for 4 h at the same temp

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

Procedure: To a solution of 1,3-dibromo-2-ethyl-benzene (30 g, 113.65 mmol) in THF (150 mL) was added 45.5 mL of BuLi (2.5M in hexane, 113.65 mmol) under nitrogen. The mixture was stirred for 4 hr at −78° C. Then N-benzyl-4-piperidone (21.51 g, 113.65 mmol) was added to the above mixture and stirred overnight, The mixture was poured into sat. aqueous NH4Cl solution and extracted with DCM. The organic layer was separated, dried over Na2SO4, and concentrated under reduced pressure give the crude 1-benzyl-4-(3-bromo-2-ethyl-phenyl)-piperidin-4-ol (D116) (30.4 g). MS (ES): C20H24BrNO requires 373. found 374 (M+H+). stirred overnight extracted with DCM The organic layer was separated dried over Na2SO4 concentrated under reduced pressure

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

Procedure: A three necked round-bottom flask was purged with argon and then filled with dry THF (1.2 l), 1,3-dibromo benzene (121 g, 0.514 mol) and ethyl iodide (95.4 g, 0.611 mol). The mixture was cooled to −78° C. and LDA (64.2 g, 0.697 mol) (2 M in THF/n-heptane/ethyl benzene) was added slowly in a way that the temperature did not rise above −65° C. After stirring for 2.75 h the reaction was poured onto 1 l sat. aq. NH4Cl solution and stirred vigorously for 20 min. Two times extraction with DCM yielded colorless oil (167 g) which was used in the next step without further purification. A three necked round-bottom flask was purged with argon did not rise above −65° C stirred vigorously for 20 min Two times extraction with DCM yielded colorless oil (167 g) which was used in the next step without further purification

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

Procedure: A three necked round-bottom flask was purged with argon and then filled with dry THF (1.2 I), 1,3-dibromo benzene (121 g, 0.514 mol) and ethyl iodide (95.4 g, 0.611 mol). The mixture was cooled to −78° C. and LDA (64.2 g, 0.697 mol) (2 M in THF/n-heptane/ethylbenzene) was added slowly in a way that the temperature didn't rise above −65° C. After stirring for 2.75 h the reaction was poured onto 11 sat. aq NH4Cl solution and stirred vigorously for 20 min. Extraction with DCM (twice) yielded a colorless oil (167 g) which was used in the next step without further purification A three necked round-bottom flask was purged with argon rise above −65° C stirred vigorously for 20 min Extraction with DCM (twice)