Sodium hydride → (4aS,7aR)-1-(5-Phenylethynyl-pyridin-2-yl)-hexahydro-cyclopenta[d][1,3]oxazin-2-one

HRID 1507134Notes

Reaction equation

HRID 1507134 reaction equation
[NH:1]1[C@@H:6]2[CH2:7][CH2:8][CH2:9][C@@H:5]2[CH2:4][O:3][C:2]1=[O:10].F[C:12]1[CH:17]=[CH:16][C:15]([C:18]#[C:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:14][N:13]=1.[H-].[Na+]>CN(C=O)C>[C:20]1([C:19]#[C:18][C:15]2[CH:16]=[CH:17][C:12]([N:1]3[C@@H:6]4[CH2:7][CH2:8][CH2:9][C@@H:5]4[CH2:4][O:3][C:2]3=[O:10])=[N:13][CH:14]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 117871704(4aS,7aR)-Hexahydro-cyclopenta[d][1,3]oxazin-2-oneHCID 1178732652-Fluoro-5-phenylethynylpyridine

Product 1

HCID 73670555(4aS,7aR)-1-(5-Phenylethynyl-pyridin-2-yl)-hexahydro-cyclopenta[d][1,3]oxazin-2-oneYield 23.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 10 ml Round bottomed flask were dissolved (4aS,7aR)-hexahydro-cyclopenta[d]-[1,3]oxazin-2-one (80 mg, 0.57 mmol, 1.0 equiv.) and 2-fluoro-5-(phenylethynyl)pyridine (112 mg, 0.57 mmol, 1.0 equiv.) in 2 ml of DMF. Sodium hydride (60% suspension) (29.5 mg, 0.74 mmol, 1.3 equiv.) were added and the brown suspension was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted twice with ethyl acetate. The combined organic phases were dried, filtered and concentrated. The crude material was purified by flash chromatography over a prepacked silica column eluting with 0-50% ethyl acetate in heptane gradient to yield 42.5 mg of the title compound as colorless amorphous solid, MS: m/e=319.1 (M+H+).

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted twice with ethyl acetate
  3. customThe combined organic phases were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography over a prepacked silica column
  7. washeluting with 0-50% ethyl acetate in heptane gradient

Sources & evidence

ORD record
ord-e7e1a687cbd94d2d98c06eb9105cb46d
Source dataset
uspto-grants-2015_12
Patent number
US09221802B2

Reaction notes

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