Sodium hydride → 9-[4-(5-Cyano-pyridin-2-yloxymethyl)-3,3-dimethyl-2-oxo-pyrrolidin-1-yl]-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester

HRID 16222

Reaction equation

HRID 16222 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([CH:7]1[CH2:14][CH:13]2[CH:15]([N:16]3[CH2:20][CH:19]([CH2:21][OH:22])[C:18]([CH3:24])([CH3:23])[C:17]3=[O:25])[CH:9]([CH2:10][CH2:11][CH2:12]2)[CH2:8]1)=[O:6].Cl[C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][N:28]=1>O1CCCC1.CN1CCCN(C)C1=O>[CH3:3][O:4][C:5]([CH:7]1[CH2:14][CH:13]2[CH:15]([N:16]3[CH2:20][CH:19]([CH2:21][O:22][C:27]4[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][N:28]=4)[C:18]([CH3:23])([CH3:24])[C:17]3=[O:25])[CH:9]([CH2:10][CH2:11][CH2:12]2)[CH2:8]1)=[O:6]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 666569529-(4-Hydroxymethyl-3,3-dimethyl-2-oxo-pyrrolidin-1-yl)-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester

Product 1

HCID 666569249-[4-(5-Cyano-pyridin-2-yloxymethyl)-3,3-dimethyl-2-oxo-pyrrolidin-1-yl]-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

NaH (0.1 g, 60% in oil, 2.56 mmol) was added in one portion to a stirred and cooled (0° C.) solution of the product of Example 7D (0.48 g, 1.42 mmol) and 6-chloro-nicotinonitrile (0.35 g, 2.56 mmol) in tetrahydrofuran (7 ml) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (7 mL). After the addition, the solution was warmed to room temperature and stirred for another five hours. The dark brown reaction mixture was cooled (0° C.), quenched with acetic acid (0.1 mL), and partitioned with diethyl ether and water. The organic phase was washed with water and brine, dried (MgSO4), filtered, and evaporated. The residue was purified over silica gel using 5-80% ethyl acetate in hexanes to give the titled product as a solid.

Workup

  1. additionAfter the addition
  2. stirringstirred for another five hours
  3. temperatureThe dark brown reaction mixture was cooled (0° C.)
  4. customquenched with acetic acid (0.1 mL)
  5. custompartitioned with diethyl ether and water
  6. washThe organic phase was washed with water and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified over silica gel using 5-80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-12166c3d0fd24dd2a46056d22bd7f91a
Source dataset
uspto-grants-2010_06
Patent number
US07737137B2

Linked notes

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