HCID 66642878, compound → HCID 66642863, compound

HRID 1171004Notes

Reaction equation

HRID 1171004 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:11][CH2:12][O:13][CH3:14])=[C:6]([N:8]([CH3:10])[CH3:9])[CH:7]=1.[Li]CCCC.[CH3:20][C:21]1[CH:28]=[C:27]([O:29][Si:30]([CH:37]([CH3:39])[CH3:38])([CH:34]([CH3:36])[CH3:35])[CH:31]([CH3:33])[CH3:32])[CH:26]=[C:25]([CH3:40])[C:22]=1[CH:23]=[O:24]>C1COCC1>[CH3:9][N:8]([CH3:10])[C:6]1[CH:7]=[C:2]([CH:23]([C:22]2[C:25]([CH3:40])=[CH:26][C:27]([O:29][Si:30]([CH:31]([CH3:33])[CH3:32])([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:36])[CH3:35])=[CH:28][C:21]=2[CH3:20])[OH:24])[CH:3]=[CH:4][C:5]=1[O:11][CH2:12][O:13][CH3:14]

Participants

5

Reactant 3

HCID 66642878HCID 66642878, compoundHCID 85783001HCID 85783001, compoundHCID 178418339Butyllithium

Product 1

HCID 66642863HCID 66642863, compoundYield 69.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirring solution of N-(5-bromo-2-methoxymethoxy-phenyl)dimethylamine (3.4 g, 13.07 mmol) in THF (80 mL) at −78° C. was added n-BuLi (5.22 mL, 2.5 M in hexanes). The mixture was stirred at −78° C. for 1 hr and a solution of 2,6-dimethyl-4-triisopropylsilanyloxy-benzaldehyde (3.6 g, 11.77 mmol) was added. The reaction mixture was stirred at −78° C. for 1 hr, allowed to warm to room temperature and stirred for 1 hr. The reaction mixture was quenched with saturated NH4Cl and diluted with diethyl ether. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, eluting with ethyl acetate-hexanes (30:70) to afford (3-dimethylamino-4-methoxymethoxy-phenyl)-(2,6-dimethyl-4-triisopropylsilanyloxyphenyl)methanol as a yellow oil (4 g, 63%): 1H NMR (300 MHz, DMSO-d6): δ 6.89 (d, J=8.4 Hz, 1 H), 6.79 (s, 1 H), 6.61 (m, 1 H), 6.51 (s, 2 H), 6.01 (d, J=4.0 Hz, 1 H), 5.65 (d, J=4.0 Hz, 1 H), 5.14 (s, 2 H), 3.41 (s, 3 H), 2.64 (s, 6 H), 2.17 (s, 6 H), 1.24 (m, 3 H), 1.08 (d, J=7.2 Hz, 18 H); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=25% ethyl acetate in hexanes; Rf=0.27.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 1 hr
  2. temperatureto warm to room temperature
  3. stirringstirred for 1 hr
  4. customThe reaction mixture was quenched with saturated NH4Cl
  5. additiondiluted with diethyl ether
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography on silica gel
  10. washeluting with ethyl acetate-hexanes (30:70)

Sources & evidence

ORD record
ord-9293cb6d354446fca22a840f34884906
Source dataset
uspto-grants-2010_11
Patent number
US07829552B2

Reaction notes

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