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

HRID 2052951

反応式

HRID 2052951 の反応式
[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]

参加物

5

反応物 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

生成物 1

HCID 69020248(4-{(R)-2-[(E)-4-(3-chlorophenyl)-3-oxo-but-1-enyl]-6-oxo-piperidin-1-yl}-butoxy)-acetic acid ethyl ester収率 34%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-c973bdcc60b7485eb800657b57fcf489
出典データセット
uspto-grants-2008_02
特許番号
US07326716B2

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