3,4-dihydro-2H-pyran → 2-phenyl-1-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]butan-1-one

HRID 2118206Notes

Reaction equation

HRID 2118206 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:18])[CH:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:10][CH3:11])=[CH:4][CH:3]=1.[O:19]1[CH:24]=[CH:23][CH2:22][CH2:21][CH2:20]1.[Cl-].[Cl-].[Ca+2]>ClCCCl>[C:12]1([CH:9]([CH2:10][CH3:11])[C:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][CH:20]3[CH2:21][CH2:22][CH2:23][CH2:24][O:19]3)=[CH:7][CH:6]=2)=[O:18])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 2272781-(4-Hydroxyphenyl)-2-phenylbutan-1-oneHCID 5284359Calcium Chloride

Product 1

HCID 148846752-phenyl-1-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]butan-1-oneYield 93%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of compound 8 (908 g, 3.78 mol) in 1,2-dichloroethane (6.36 L) stirred at 30° C. was treated with dihydropyran (1590 g, 18.9 mol) in a single portion. The resulting solution was treated with CaCl2 (83.8 g, 0.76 mmol) in a single portion and the reaction warmed at 70° C. for 16 h. The reaction was filtered through celite and the solid washed with 1,2-dichloroethane (2×900 mL). The filtrate was concentrated by distillation to approximately 5 L and heptane added (9 L). The reaction solution was again concentrated by distillation to approximately 7 L and then cooled slowly and held at 5° C. for 1 h. The solids were filtered, washed with heptane (2×1.8 L) and dried in vacuo at 40° C. to afford 1134 g (93%) of 9 as a solid. 1HNMR (400 MHz, DMSO-d6): δ 0.79 (t, J=7.3 Hz, 3H), 1.49-1.83 (m, 8H), 2.03 (h, J=7.0 Hz, 1H), 3.49-3.66 (m, 2H), 4.65 (t, J=7.2 Hz, 1H), 7.02 (d, J=8.4 Hz, 2H), 7.13-7.30 (m, 5H), 7.97 (d, J=8.4 Hz, 2H).

Workup

  1. temperaturethe reaction warmed at 70° C. for 16 h
  2. filtrationThe reaction was filtered through celite
  3. washthe solid washed with 1,2-dichloroethane (2×900 mL)
  4. concentrationThe filtrate was concentrated by distillation to approximately 5 L and heptane
  5. additionadded (9 L)
  6. concentrationThe reaction solution was again concentrated by distillation to approximately 7 L
  7. temperaturecooled slowly
  8. filtrationThe solids were filtered
  9. washwashed with heptane (2×1.8 L)
  10. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-a46048a433644c1cb95f9c93f6cfb229
Source dataset
uspto-grants-2008_10
Patent number
US07442833B2

Reaction notes

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