Sodium hydride → 2-(3-Chloro-4-cyano-2-methylbenzyl)-1-oxo-octahydrocyclopenta[c]-pyrrol-4-yl benzoate

HRID 15191

反応式

HRID 15191 の反応式
[C:1]([O:9][CH:10]1[CH:17]2[CH:13]([C:14](=[O:18])[NH:15][CH2:16]2)[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C(C)=C(N2C[C@@H]3[C@H](O)CC[C@@H]3C2=O)C=CC=1C#N.[H-].[Na+].Br[CH2:42][C:43]1[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[C:45]([Cl:51])[C:44]=1[CH3:52]>C1COCC1.CN(C=O)C>[C:1]([O:9][CH:10]1[CH:17]2[CH:13]([C:14](=[O:18])[N:15]([CH2:42][C:43]3[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[C:45]([Cl:51])[C:44]=3[CH3:52])[CH2:16]2)[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:1]([O:9][CH:10]1[CH:17]2[CH:16]([N:15]([CH2:42][C:43]3[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[C:45]([Cl:51])[C:44]=3[CH3:52])[C:14](=[O:18])[CH2:13]2)[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

8

反応物 4

HCID 24758Sodium hydrideHCID 112200114-[(3aR,4R,6aS)-4-hydroxy-1-oxo-octahydrocyclopenta[c]pyrrol-2-yl]-2-chloro-3-methylbenzonitrileHCID 592595601-Oxo-octahydrocyclopenta[c]pyrrol-4-yl benzoateHCID 685774134-(Bromomethyl)-2-chloro-3-methylbenzonitrile

生成物 2

HCID 592595572-(3-Chloro-4-cyano-2-methylbenzyl)-1-oxo-octahydrocyclopenta[c]-pyrrol-4-yl benzoateHCID 592595681-(3-Chloro-4-cyano-2-methylbenzyl)-2-oxo-octahydrocyclopenta[b]-pyrrol-4-yl benzoate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution containing mixtures of compound 1I and 1J (170 mg, 0.69 mmol, different batch than previous lot in example 1) in anhydrous THF (4 mL) and anhydrous DMF (4 mL) was added sodium hydride (27.7 mg, 0.69 mmol) at 0° C., and stirred at 0° C. for 45 min. Compound 7C (169 mg, 0.69 mmol) was added at 0° C., the ice-water bath was removed, and the stirring was continued between 0° C. to RT for 2 hr before it was quenched with saturated NH4Cl solution. The mixture was diluted with EtOAc, organic layer was separated, washed with water, dried over MgSO4, and concentrated. Purification by silica gel chromatography (30-100% EtOAc in hexanes) provide the title compound 7D (90 mg) and 7E (151 mg). Compound 7D: (ES) m/z 409 [M+H]+. Compound 7E: (ES) m/z 409 [M+H]+.

後処理

  1. customthe ice-water bath was removed
  2. waitthe stirring was continued between 0° C. to RT for 2 hr before it
  3. customwas quenched with saturated NH4Cl solution
  4. additionThe mixture was diluted with EtOAc, organic layer
  5. customwas separated
  6. washwashed with water
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (30-100% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-91fdaf33f4db4b739f6eeeb94f2df395
出典データセット
uspto-grants-2010_06
特許番号
US07732480B2

関連ノート

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