1-[2-(4-Bromophenoxy)ethyl]piperidine → 5-(tert-butyl-dimethyl-silyloxy)-2-(7-(tert-butyl-dimethyl-silyloxy)-4-{1-hydroxy-1-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-ethyl}-2H-chromen-3-yl)-phenol

HRID 2214300Notes

Reaction equation

HRID 2214300 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[CH2:17]([Li])CCC.[C:22]([Si:26]([CH3:56])([CH3:55])[O:27][C:28]1[CH:29]=[CH:30][C:31]2[C:32]3[C:45](=[O:46])[O:44][C:43]4[CH:42]=[C:41]([O:47][Si:48]([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49])[CH:40]=[CH:39][C:38]=4[C:33]=3[CH2:34][O:35][C:36]=2[CH:37]=1)([CH3:25])([CH3:24])[CH3:23].C[Mg]Br>C1COCC1>[C:51]([Si:48]([CH3:50])([CH3:49])[O:47][C:41]1[CH:40]=[CH:39][C:38]([C:33]2[CH2:34][O:35][C:36]3[C:31]([C:32]=2[C:45]([OH:46])([C:2]2[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH2:8][N:9]4[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]4)=[CH:4][CH:3]=2)[CH3:17])=[CH:30][CH:29]=[C:28]([O:27][Si:26]([C:22]([CH3:23])([CH3:25])[CH3:24])([CH3:55])[CH3:56])[CH:37]=3)=[C:43]([OH:44])[CH:42]=1)([CH3:54])([CH3:52])[CH3:53]

Participants

6

Reactant 4

HCID 8671951-[2-(4-Bromophenoxy)ethyl]piperidineHCID 115915722,8-bis((tert-butyldimethylsilyl)oxy)chromeno[4,3-c]chromen-5(11H)-oneHCID 178418339ButyllithiumHCID 178418573HCID 178418573, compound

Product 1

HCID 219591825-(tert-butyl-dimethyl-silyloxy)-2-(7-(tert-butyl-dimethyl-silyloxy)-4-{1-hydroxy-1-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-ethyl}-2H-chromen-3-yl)-phenol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-[2-(4-bromophenoxy)-ethyl]-piperidine (360 mg, 1.27 mmol) in THF (7.5 mL) at −78° C., was added n-butyl lithium (1.6 M in hexane, 773 μL, 1.24 mmol). The reaction mixture was stirred at −78° C. for 0.5 hours. To the reaction mixture was then added 2,8-bis-(tert-butyl-dimethyl-silyloxy)-11H-chromeno[4,3-c]chromen-5-one, prepared as in Example 22, (158 mg, 0.31 mmol) in THF (3 mL) and the mixture was stirred at −78° C. for 1.5 hours. To the reaction mixture was then added methyl magnesium bromide (3 M in diethyl ether, 1 mL, 3 mmol) at −78° C. and the reaction 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 organic layer was concentrated to yield the crude title product as a yellow oil, which was carried into the next step without further purification.

Workup

  1. stirringthe mixture was stirred at −78° C. for 1.5 hours
  2. customThe reaction was quenched with aqueous NH4Cl
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-21e9745b413c4ebea06cdd3bfd65b000
Source dataset
uspto-grants-2006_09
Patent number
US07105679B2

Reaction notes

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