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

HRID 15191

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HRID 15191 반응식
[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

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-91fdaf33f4db4b739f6eeeb94f2df395
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732480B2

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