2,8-bis((tert-butyldimethylsilyl)oxy)chromeno[4,3-c]chromen-5(11H)-one → 2-[4-{-1-[4-(2-azepan-1-yl-ethoxy)-phenyl]-1-hydroxy-ethyl}-7-(tert-butyl-dimehyl-silyloxy)-2H-chromen-3-yl]-5-(tert-butyl-dimethyl-silyloxy)-phenol

HRID 2055039Notes

Reaction equation

HRID 2055039 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[CH2:18]([Li])CCC.[C:23]([Si:27]([CH3:57])([CH3:56])[O:28][C:29]1[CH:30]=[CH:31][C:32]2[C:33]3[C:46](=[O:47])[O:45][C:44]4[CH:43]=[C:42]([O:48][Si:49]([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50])[CH:41]=[CH:40][C:39]=4[C:34]=3[CH2:35][O:36][C:37]=2[CH:38]=1)([CH3:26])([CH3:25])[CH3:24].C[Mg]Br>C1COCC1>[N:9]1([CH2:8][CH2:7][O:6][C:5]2[CH:16]=[CH:17][C:2]([C:46]([C:33]3[C:32]4[C:37](=[CH:38][C:29]([O:28][Si:27]([C:23]([CH3:25])([CH3:24])[CH3:26])([CH3:56])[CH3:57])=[CH:30][CH:31]=4)[O:36][CH2:35][C:34]=3[C:39]3[CH:40]=[CH:41][C:42]([O:48][Si:49]([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50])=[CH:43][C:44]=3[OH:45])([OH:47])[CH3:18])=[CH:3][CH:4]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 115915722,8-bis((tert-butyldimethylsilyl)oxy)chromeno[4,3-c]chromen-5(11H)-oneHCID 130635441-[2-(4-Bromophenoxy)ethyl]azepaneHCID 178418339ButyllithiumHCID 178418573HCID 178418573, compound

Product 1

HCID 693277712-[4-{-1-[4-(2-azepan-1-yl-ethoxy)-phenyl]-1-hydroxy-ethyl}-7-(tert-butyl-dimehyl-silyloxy)-2H-chromen-3-yl]-5-(tert-butyl-dimethyl-silyloxy)-phenol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-[2-(4-bromophenoxy)ethyl]-azepane (356 mg, 1.19 mmol) in THF (7.5 mL) at −78° C., was added n-butyl lithium (2.5 M in hexane, 466 μL, 1.17 mmol). The reaction mixture was stirred at −78° C. for 0.5 hours. To the mixture was then added 2,8-bis-(tert-butyl-dimethyl-silyloxy)-11H-chromeno[4,3-c]chromen-5-one, prepared as in Example 22, (149 mg, 0.29 mmol) in THF (3 mL) and the reaction mixture stirred at −78° C. for 1.5 hours. To the mixture was then methyl magnesium bromide (3 M in diethyl ether, 1 mL, 3 mmol) at −78° C. and then 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 remaining solvent was evaporated to yield the crude title product as a yellow oil, which was carried on to the next step without further purification.

Workup

  1. stirringthe reaction mixture 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. customThe remaining solvent was evaporated

Sources & evidence

ORD record
ord-f825f03942624639915b9b7a627893ce
Source dataset
uspto-grants-2008_02
Patent number
US07329654B2

Reaction notes

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