1-Bromo-4-(diethoxymethyl)benzene → 4-[(1Z)-1-(4-Hydroxyphenyl)-2-phenylbut-1-enyl]benzaldehyde

HRID 2118207Notes

Reaction equation

HRID 2118207 reaction equation
CCO[CH:4]([O:12]CC)[C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1.[Li]CCCC.[C:20]1([CH:26]([CH2:42][CH3:43])[C:27]([C:29]2[CH:34]=[CH:33][C:32]([O:35]C3CCCCO3)=[CH:31][CH:30]=2)=O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[OH:35][C:32]1[CH:31]=[CH:30][C:29](/[C:27](/[C:8]2[CH:7]=[CH:6][C:5]([CH:4]=[O:12])=[CH:10][CH:9]=2)=[C:26](\[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)/[CH2:42][CH3:43])=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 6883401-Bromo-4-(diethoxymethyl)benzeneHCID 148846752-phenyl-1-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]butan-1-oneHCID 178418339Butyllithium

Product 1

HCID 588776594-[(1Z)-1-(4-Hydroxyphenyl)-2-phenylbut-1-enyl]benzaldehydeYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-65 °C

Procedure

A three-neck flask equipped with mechanical stirrer, thermometer, and nitrogen inlet was charged with 4-bromobenzaldehydediethyl acetal (800 g, 2.47 mol) and THF (7.2 L). The contents were cooled to −65° C. and treated with a 2.5M solution of n-BuLi in hexanes (1.23, 3.08 mol) at a rate to maintain temperature <−65° C. The solution was then treated with a solution of 9 (800 g, 2.47 mol) in THF (2.4 L) at a rate to maintain temperature <−65° C. The resulting solution was allowed to warm to ambient temperature over a 1 h period. At 20° C. the reaction was quenched by addition of a saturated aqueous NH4Cl solution (4 L) followed by EtOAc (4 L). After mixing well, the lower aqueous layer was separated and the organic layer washed with H2O (2×4 L). The organic layer was evaporated under reduced pressure to approximately 4 L. tert-BuOH (8 L) was added and evaporation continued to a volume of approximately 4 L. The solution was heated to 65° C. and treated with 3 N aqueous HCl (80 mL) and maintained at 65° C. for approximately 1 h. The reaction solution was diluted with heptane (8 L) and then cooled slowly to 5° C. and maintained for 1 h. The solids were collected by filtration, washed with heptane (2×1.5 L), and dried in vacuo at 40° C. to afford 511 g of 10 (63%) as a 98:2 mixture of Z:E isomers. 1HNMR (400 MHz, DMSO-d6): δ 0.83 (t, J=7.3 Hz, 3H), 2.33 (q, J=7.3 Hz, 2H), 6.41 (d, J=8.4 Hz, 2H), 6.60 (d, J=8.4 Hz, 2H), 7.10-7.20 (m, 5H), 7.40 (d, J=8.1 Hz, 2H), 7.90 (d, J=8.0 Hz, 2H), 9.25 (s, 1H), 9.98 (s, 1H).

Workup

  1. customA three-neck flask equipped with mechanical stirrer
  2. temperatureto maintain temperature <−65° C
  3. temperatureto maintain temperature <−65° C
  4. temperatureto warm to ambient temperature over a 1 h period
  5. customAt 20° C. the reaction was quenched by addition of a saturated aqueous NH4Cl solution (4 L)
  6. additionAfter mixing well
  7. customthe lower aqueous layer was separated
  8. washthe organic layer washed with H2O (2×4 L)
  9. customThe organic layer was evaporated under reduced pressure to approximately 4 L
  10. additiontert-BuOH (8 L) was added
  11. customevaporation
  12. temperatureThe solution was heated to 65° C.
  13. additiontreated with 3 N aqueous HCl (80 mL)
  14. temperaturemaintained at 65° C. for approximately 1 h
  15. additionThe reaction solution was diluted with heptane (8 L)
  16. temperaturecooled slowly to 5° C.
  17. temperaturemaintained for 1 h
  18. filtrationThe solids were collected by filtration
  19. washwashed with heptane (2×1.5 L)
  20. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-001930e5bbff4043aea4164fa21f4405
Source dataset
uspto-grants-2008_10
Patent number
US07442833B2

Reaction notes

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