Sodium Chloride → ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-fluoro-3-pyridinyl)acrylate

HRID 226456

Reaction equation

HRID 226456 reaction equation
[H-].[Na+].COP([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(OC)=O.[CH2:15]([N:22]1[CH2:26][CH2:25][C@@H:24]([NH:27][C:28]2[C:35]([F:36])=[CH:34][C:31]([CH:32]=O)=[CH:30][N:29]=2)[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[Na+].[Cl-]>C1COCC1.CCOC(C)=O>[CH2:15]([N:22]1[CH2:26][CH2:25][C@@H:24]([NH:27][C:28]2[N:29]=[CH:30][C:31](/[CH:32]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:34][C:35]=2[F:36])[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 67555Ethyl (dimethoxyphosphinoyl)acetateHCID 866037566-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-fluoronicotinaldehyde

Product 1

HCID 86603762ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-fluoro-3-pyridinyl)acrylateYield 36%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
24 °C

Procedure

To an ice-cooled suspension of sodium hydride (38.5 mg) in THF (10 ml) was added ethyl (dimethoxyphosphoryl)acetate (206 mg), and the mixture was stirred at 24° C. for 40 minutes. To the mixture was added 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-fluoronicotinaldehyde (250 mg) at 24° C., the reaction mixture was stirred at same temperature for 30 minutes. The reaction mixture was poured into a mixture of AcOEt and 5% aqueous NaCl. The separated organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (8.2 g) using a mixed solvent of CH2Cl2 and MeOH(100:1 to 35:1). The fractions containing the objective compound were collected and evaporated under reduced pressure. Title compound (111 mg, 36%) was obtained as oil.

Workup

  1. stirringthe reaction mixture was stirred at same temperature for 30 minutes
  2. washThe separated organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated in vacuo
  5. customThe resulting residue was purified by column chromatography on silica gel (8.2 g)
  6. additionThe fractions containing the objective compound
  7. customwere collected
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-53aa52e0cdf54b7fb1370e648422767d
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Linked notes

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