N-(2-(p-bromophenoxy)ethyl)pyrrolidine → 5-(Tert-butyl-dimethyl-silyloxy)-2-(7-(tert-butyl-dimethyl-silyloxy)-4-{1-hydroxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-ethyl}-2H-chromen-3-yl)phenol

HRID 2055036Notes

Reaction equation

Br[C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[CH2:16]([Li])CCC.[C:21]([Si:25]([CH3:55])([CH3:54])[O:26][C:27]1[CH:28]=[CH:29][C:30]2[C:31]3[C:44](=[O:45])[O:43][C:42]4[CH:41]=[C:40]([O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])[CH:39]=[CH:38][C:37]=4[C:32]=3[CH2:33][O:34][C:35]=2[CH:36]=1)([CH3:24])([CH3:23])[CH3:22].C[Mg]Br>C1COCC1>[C:50]([Si:47]([CH3:49])([CH3:48])[O:46][C:40]1[CH:39]=[CH:38][C:37]([C:32]2[CH2:33][O:34][C:35]3[C:30]([C:31]=2[C:44]([OH:45])([C:2]2[CH:15]=[CH:14][C:5]([O:6][CH2:7][CH2:8][N:9]4[CH2:13][CH2:12][CH2:11][CH2:10]4)=[CH:4][CH:3]=2)[CH3:16])=[CH:29][CH:28]=[C:27]([O:26][Si:25]([C:21]([CH3:23])([CH3:24])[CH3:22])([CH3:55])[CH3:54])[CH:36]=3)=[C:42]([OH:43])[CH:41]=1)([CH3:51])([CH3:52])[CH3:53]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-[2-(4-bromophenoxy)-ethyl]-pyrrolidine (331 mg, 1.22 mmol) in THF (7.5 mL) at −78° C., was added n-butyl lithium (2.5 M in hexane, 478 μL, 1.19 mmol). The mixture was stirred at −78° C. for 0.5 hours. To this mixture was then added 2,8-bis-(tert-butyl-dimethyl-silyloxy)-11H-chromeno[4,3-c]chromen-5-one (153 mg, 0.30 mmol) in THF (3 mL), prepared as in Example 22. The reaction mixture was then stirred at −78° C. for 1.5 hours. To this mixture was added methyl magnesium bromide (3 M in diethyl ether, 1 mL, 2.99 mmol) at −78° C. and the reaction mixture stirred at room temperature overnight. The reaction was quenched with aqueous NH4Cl and extracted with ethyl acetate. The organic layer was washed with brine and dried over MgSO4. The solvent was evaporated to yield the crude product as a yellow oil. The crude product was carried to the next step without further purification.

Workup

stirringThe reaction mixture was then stirred at −78° C. for 1.5 hours
stirringthe reaction mixture stirred at room temperature overnight
customThe reaction was quenched with aqueous NH4Cl
extractionextracted with ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over MgSO4
customThe solvent was evaporated

Sources & evidence

ORD record: ord-85ce62f17f214de8864a5ce197c03095
Source dataset: uspto-grants-2008_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07329654B2

Reaction notes

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