3,4-dihydro-2H-pyran → HCID 66978150, compound

HRID 1631056Notes

Reaction equation

HRID 1631056 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7]([CH2:15][CH2:16][C:17]([OH:19])=O)([CH3:14])[CH2:6][CH2:5]2.[O:20]1[CH:25]=[CH:24][CH2:23][CH2:22][CH2:21]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>ClCCl.C1COCC1>[CH3:14][C:7]1([CH2:15][CH2:16][CH2:17][OH:19])[CH2:6][CH2:5][C:4]2[C:9](=[C:10]([CH3:13])[C:11]([CH3:12])=[C:2]([O:1][CH:21]3[CH2:22][CH2:23][CH2:24][CH2:25][O:20]3)[CH:3]=2)[O:8]1

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 1330982,7,8-Trimethyl-2-(beta-carboxy-ethyl)-6-hydroxychromanHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)

Product 1

HCID 66978150HCID 66978150, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(6-hydroxy-2,7,8-trimethyl-chroman-2-yl)-propionic acid (500 mg), 3,4-dihydro-2-H-pyran (2 mL) and pyridinium p-toluenesulfonate (PPTS) (50 mg) in dichloromethane (20 mL) was stirred at RT for overnight. The mixture was washed with water, dried over MgSO4, and concentrated to give an oily residue. The oil was dissolved in THF, then LiAIH4 (85 mg) was added and the mixture was stirred at RT for 2 h. The excess LiAIH4 was destroyed by adding ethyl acetate, and the mixture was poured into water and extracted with EtOAc. The organic layer was washed with water, dried over MgSO4, and concentrated. The residue was purified by silica gel column chromatography eluting with 30% EtOAc in hexane to give 732 mg of 3-[2,7,8-trimethyl-6-(tetrahydro-pyran-2-yloxy)-chroman-2-yl]-propan-1-ol as an oily product. 1H-NMR (300 MHz, CDCl3) δ (ppm): 6.67 (s, 1H), 5.32 (t, J=3.2 MHz, 1H), 4.0-3.9 (m, 1H), 3.70-3.55 (m, 3H), 2.75-2.70 (m, 2H), 2.15, 2.09 (2s, 6H), 2.10-1.60 (m, 12H), 1.25 (s, 3H). 13C-NMR (75 MHz, CDCl3) δ (ppm): 148.08, 146.23, 125.51, 125.25, 117.66, 112.99, 112.96, 97.36, 75.17, 63.25, 62.09, 60.41, 36.26, 36.03, 31.51, 31.47, 30.78, 26.97, 25.41, 24.01, 23.81, 22.48, 21.05, 19.11, 14.19, 12.18, 11.94.

Workup

  1. washThe mixture was washed with water
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customto give an oily residue
  5. additionLiAIH4 (85 mg) was added
  6. stirringthe mixture was stirred at RT for 2 h
  7. customThe excess LiAIH4 was destroyed
  8. additionby adding ethyl acetate
  9. additionthe mixture was poured into water
  10. extractionextracted with EtOAc
  11. washThe organic layer was washed with water
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated
  14. customThe residue was purified by silica gel column chromatography
  15. washeluting with 30% EtOAc in hexane

Sources & evidence

ORD record
ord-7883c77fd35f4c22a6c795799cdda0f0
Source dataset
uspto-grants-2014_07
Patent number
US08791155B2

Reaction notes

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