Sodium hydride → HCID 69020248, compound

HRID 349348

Reaction equation

HRID 349348 reaction equation
[H-].[Na+].COP([CH2:9][C:10](=[O:19])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1)(=O)OC.[CH2:20]([O:22][C:23](=[O:39])[CH2:24][O:25][CH2:26][CH2:27][CH2:28][CH2:29][N:30]1[C:35](=[O:36])[CH2:34][CH2:33][CH2:32][C@@H:31]1[CH:37]=O)[CH3:21]>C1COCC1>[CH2:20]([O:22][C:23](=[O:39])[CH2:24][O:25][CH2:26][CH2:27][CH2:28][CH2:29][N:30]1[C:35](=[O:36])[CH2:34][CH2:33][CH2:32][C@@H:31]1/[CH:37]=[CH:9]/[C:10](=[O:19])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1)[CH3:21]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 12989750Dimethyl [3-(3-chlorophenyl)-2-oxopropyl]phosphonateHCID 86595299[4-((R)-2-formyl-6-oxo-piperidin-1-yl)-butoxy]-acetic acid ethyl ester

Product 1

HCID 69020248HCID 69020248, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 35 mg, 0.88 mmol) was added to a solution of [3-(3-chlorophenyl)-2-oxopropyl]-phosphonic acid dimethyl ester (221 mg, 0.80 mmol) in THF (2.0 mL) at 0° C. After 1 h at 0° C., [4-((R)-2-formyl-6-oxo-piperidin-1-yl)-butoxy]-acetic acid ethyl ester (0.88 mmol, crude) in THF (2 mL) was added via cannula. The reaction was allowed to warm to rt. After 18 h at rt, the reaction was quenched with aqueous acetic acid (50%, 10 mL) and extracted with EtOAc (3×20 mL). The combined organic phase was washed with brine (25 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (20% →40% EtOAc/CH2Cl2, gradient) afforded 117 mg (34%) of (4-{(R)-2-[(E)-4-(3-chlorophenyl)-3-oxo-but-1-enyl]-6-oxo-piperidin-1-yl}-butoxy)-acetic acid ethyl ester.

Workup

  1. waitAfter 18 h at rt
  2. customthe reaction was quenched with aqueous acetic acid (50%, 10 mL)
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic phase was washed with brine (25 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash column chromatography on silica gel (20% →40% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-0d6484f6104048d9a4bc30d491aac73c
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Linked notes

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