Sodium hydride → (4-{(R)-2-[(E)-4-(3-Chlorophenyl)-3-oxo-but-1-enyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl ester

HRID 489172Notes

Reaction equation

HRID 489172 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.[CH3:20][O:21][C:22](=[O:38])[CH2:23][O:24][CH2:25][C:26]#[C:27][CH2:28][N:29]1[C:34](=[O:35])[CH2:33][CH2:32][CH2:31][C@@H:30]1[CH:36]=O>C1COCC1>[CH3:20][O:21][C:22](=[O:38])[CH2:23][O:24][CH2:25][C:26]#[C:27][CH2:28][N:29]1[C:34](=[O:35])[CH2:33][CH2:32][CH2:31][C@@H:30]1/[CH:36]=[CH:9]/[C:10](=[O:19])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 12989750Dimethyl [3-(3-chlorophenyl)-2-oxopropyl]phosphonateHCID 86595300HCID 86595300, compound

Product 1

HCID 11212242(4-{(R)-2-[(E)-4-(3-Chlorophenyl)-3-oxo-but-1-enyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl esterYield 68.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 15 mg, 0.39 mmol) was added to a solution of [3-(3-chlorophenyl)-2-oxopropyl]-phosphonic acid dimethyl ester (97 mg, 0.35 mmol) in THF (1.5 mL) at 0° C. After 1 h at 0° C., a solution of [4-((R)-2-formyl-6-oxo-piperidin-1-yl)-but-2-ynyloxy]-acetic acid methyl ester (0.37 mmol, crude) in THF (1.5 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%, 15 mL) and extracted with EtOAc (3×15 mL). The combined organic phase was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (20% →30% EtOAc/CH2Cl2, gradient) afforded 100 mg (68%) of the title compound.

Workup

  1. waitAfter 18 h at rt
  2. customthe reaction was quenched with aqueous acetic acid (50%, 15 mL)
  3. extractionextracted with EtOAc (3×15 mL)
  4. washThe combined organic phase was washed with brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash column chromatography on silica gel (20% →30% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-203f103bedd945fb9bc3c4b42430edd0
Source dataset
uspto-grants-2005_12
Patent number
US06977260B2

Reaction notes

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