Phenol → 2,2-Dimethyl-5-[4-(tetrahydro-pyran-2-yloxy)-benzylidene]-[1,3]dioxane-4,6-dione

HRID 1993075Notes

Reaction equation

HRID 1993075 reaction equation
C1(O)C=CC=CC=1.[O:8]1[CH:13]=[CH:12][CH2:11][CH2:10][CH2:9]1.[OH:14][C:15]1[CH:31]=[CH:30][C:18]([CH:19]=[C:20]2[C:25](=[O:26])[O:24][C:23]([CH3:28])([CH3:27])[O:22][C:21]2=[O:29])=[CH:17][CH:16]=1>ClCCl.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>[CH3:27][C:23]1([CH3:28])[O:24][C:25](=[O:26])[C:20](=[CH:19][C:18]2[CH:30]=[CH:31][C:15]([O:14][CH:13]3[CH2:12][CH2:11][CH2:10][CH2:9][O:8]3)=[CH:16][CH:17]=2)[C:21](=[O:29])[O:22]1

Participants

6

Reactant 3

HCID 996PhenolHCID 80803,4-dihydro-2H-pyran2×HCID 3705415-(4-Hydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione

Product 1

HCID 578018192,2-Dimethyl-5-[4-(tetrahydro-pyran-2-yloxy)-benzylidene]-[1,3]dioxane-4,6-dione

Reagents, catalysts & solvents 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 6344DichloromethaneSolvent

Procedure

Protection of the phenol with dihydropyran was carried out based on the method given in Miyashita et al. (1977) J. Org. Chem. 42: 3772. Compound 1.1 (500 g, 2 mol) was dissolved in dichloromethane (4 L). 3,4-Dihydro-2H-pyran (250 g, 3 mol) was added to the suspension followed by PPTS (5 g, 20 mmol). The reaction mixture heated to a gentle reflux (3.5 h). HPLC showed ˜90% completion of the reaction. The reaction was concentrated under reduced pressure to ˜2 L of volume. 1 L of acetone was added, and 2 L of solvent was removed under reduced pressure. 1 L of acetone was added, and 1 L of solvent was removed under reduced pressure. 0.5 L of acetone was added, and 0.5 L of solvent was removed under reduced pressure. The resulting slurry of very fine, light yellow crystals was filtered and rinsed sequentially with two 500 mL portions of acetone. The product was dried in a vacuum oven at 50° C. until no further solvent collected in the traps. Compound 52.1 (528 g) was obtained as fine, light yellow crystals. 1H NMR (400 MHz)(DMSO-d6) δ 8.29 (s, 1H); 8.18 (d, 2H, J=8.9 Hz); 7.13 (d, 2H, J=8.9 Hz); 5.67 (m, 1H); 3.70 (m, 1H); 3.60 (m, 1H). 1.9-1.5 (m, 12H). MS ESI (pos.) m/e: 355.1 (M+Na).

Workup

  1. temperatureThe reaction mixture heated to
  2. temperaturea gentle reflux (3.5 h)
  3. custom˜90% completion of the reaction
  4. concentrationThe reaction was concentrated under reduced pressure to ˜2 L of volume
  5. addition1 L of acetone was added
  6. custom2 L of solvent was removed under reduced pressure
  7. addition1 L of acetone was added
  8. custom1 L of solvent was removed under reduced pressure
  9. addition0.5 L of acetone was added
  10. custom0.5 L of solvent was removed under reduced pressure
  11. filtrationThe resulting slurry of very fine, light yellow crystals was filtered
  12. washrinsed sequentially with two 500 mL portions of acetone
  13. customThe product was dried in a vacuum oven at 50° C. until no further solvent
  14. customcollected in the traps

Sources & evidence

ORD record
ord-25af71aecb254f2d8192f3643c32b62d
Source dataset
uspto-grants-2010_01
Patent number
US07649110B2

Reaction notes

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