Pyrrolidine → 5-Bromo-2-[4-(4-pyrrolidin-1-ylmethyl-phenyl)-but-1-ynyl]-pyridine

HRID 271638Notes

Reaction equation

HRID 271638 reaction equation
CS(Cl)(=O)=O.[Br:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]#[C:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23]O)=[CH:19][CH:18]=2)=[N:11][CH:12]=1.C([N:27]([CH:31]([CH3:33])C)[CH:28]([CH3:30])C)C.N1CCCC1>C(Cl)Cl>[Br:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]#[C:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][N:27]3[CH2:28][CH2:30][CH2:33][CH2:31]3)=[CH:19][CH:18]=2)=[N:11][CH:12]=1

Participants

6

Reactant 4

HCID 31268Pyrrolidine2×HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 69070552{4-[4-(5-Bromo-pyridin-2-yl)-but-3-ynyl]-phenyl}-methanol

Product 1

HCID 690713915-Bromo-2-[4-(4-pyrrolidin-1-ylmethyl-phenyl)-but-1-ynyl]-pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

0.24 mL (3.04 mmol) methanesulphonic acid chloride are added to a solution, cooled to 0° C., of 800 mg (2.53 mmol) {4-[4-(5-bromo-pyridin-2-yl)-but-3-ynyl]-phenyl}-methanol in 17 mL DCM and then a solution of 0.52 mL ethyldiisopropylamine in 3 mL DCM is added dropwise. The mixture is stirred for a further 30 min at 0° C., 0.51 mL (6.08 mmol) pyrrolidine is added, the reaction mixture is heated to RT and kept at this temperature for 5 h. To complete the reaction another 0.26 mL (3 mmol) pyrrolidine are added and stirred for 1 h at RT. The mixture is evaporated down i.vac., combined with 10 mL water and 20 ml EtOAc, acidified with 1 M HCl and the organic phase is separated off. The aqueous phase is made alkaline with 2 M Na2CO3 solution, extracted with 20 mL EtOAc, the organic phase is separated off and dried over Na2SO4. After the desiccant and solvent have been eliminated the desired product is obtained.

Workup

  1. temperaturethe reaction mixture is heated to RT
  2. waitkept at this temperature for 5 h
  3. additionare added
  4. stirringstirred for 1 h at RT
  5. customThe mixture is evaporated down i.vac
  6. customthe organic phase is separated off
  7. extractionextracted with 20 mL EtOAc
  8. customthe organic phase is separated off
  9. dry with materialdried over Na2SO4
  10. customis obtained

Sources & evidence

ORD record
ord-9d62424f6eba4cb48ad416fb957acb80
Source dataset
uspto-grants-2008_11
Patent number
US07452911B2

Reaction notes

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