Butyl bromide → (6-Butoxy-pyridin-3-yl)-(S)(+)-(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone

HRID 552585Notes

Reaction equation

HRID 552585 reaction equation
[OH:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:9])=[CH:4][CH:3]=1.Br[CH2:22][CH2:23][CH2:24][CH3:25].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(Cl)Cl>[CH2:22]([O:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:9])=[CH:4][CH:3]=1)[CH2:23][CH2:24][CH3:25]

Participants

6

Reactant 3

HCID 8002Butyl bromideHCID 10796Cesium carbonateHCID 178519724(6-Hydroxy-pyridin-3-yl)-(S)(+)-(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone

Product 1

HCID 11960840(6-Butoxy-pyridin-3-yl)-(S)(+)-(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanoneYield 50.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (6-hydroxy-pyridin-3-yl)-(S)(+)-(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone (85 mg, 0.31 mmol), 1-bromo butane (0.04 mL, 0.36 mmol), cesium carbonate (195 mg, 0.60 mmol), and catalytic KI in dioxane (5 mL) is stirred under nitrogen at 80-90° C. for 10 h. The reaction is diluted with CH2Cl2, filtered, and washed with brine. The organic portion is dried over Na2SO4, filtered and evaporated. The crude product is partially purified by a SCX column (MeOH wash, elution with 2M NH3 in MeOH. Further purification is accomplished using silica-gel column chromatography (gradient: 100% CH2Cl2 to 10% 2M NH3 in MeOH/CH2Cl2) to give the title compound (52 mg, 50%). MS (ES+) 332.2 (M+H)+.

Workup

  1. filtrationfiltered
  2. washwashed with brine
  3. dry with materialThe organic portion is dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product is partially purified by a SCX column (MeOH
  7. washwash
  8. washelution with 2M NH3 in MeOH
  9. customFurther purification

Sources & evidence

ORD record
ord-0277d172b47b4672af4557fc45a2b3b5
Source dataset
uspto-grants-2011_05
Patent number
US07951826B2

Reaction notes

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