Acetic Acid → Coumarin

HRID 975538Notes

Reaction equation

HRID 975538 reaction equation
[Si](O[C@H]1[C:18]2[C:17]3[O:19][C:20](=[O:26])[CH:21]=[C:22](CCC)[C:16]=3[C:15]3OC(C)(C)C=C[C:14]=3[C:13]=2O[C@H](C)[C@H]1C)(C(C)(C)C)(C)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-].CCN(CC)CC.CC(O)=O>C1COCC1.CCOC(C)=O.CC(O)=O.CCN(CC)CC>[O:19]1[C:17]2[C:16](=[CH:15][CH:14]=[CH:13][CH:18]=2)[CH:22]=[CH:21][C:20]1=[O:26]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 384860(-)-(12R)-tert-Butyldimethylsiyloxy-6,11R)-dimethyl-4-propyl-6,10,11,12-tetrahydrodipyrano[2,3-fHCID 2724141Tetrabutylammonium Fluoride

Product 1

HCID 323CoumarinYield 208.5%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 165295Triethylamine acetateSolvent

Procedure

To a solution of 11 (622 mg, 1.28 mmol) in THF (25 mL) was added Bu4NF (12.5 mL, 1 M solution in THF), and the reaction mixture was stirred for 20 min. A mixture of Et3N (65 mg, 0.064 mmol) and HOAc (44 mg, 0.73 mmol) in THF (1.5 mL) was then added, and stirring was continued. The HOAc-Et3N addition was repeated after 2 h, and the reaction was stirred an additional 5 h, after which time the solvent was evaporated. The syrup obtained was then dissolved in EtOAc (30 mL) and washed with water (30 mL). The aqueous layer was separated and extracted with EtOAc (2×30 mL). The combined organic layers were dried (MgSO4) and concentrated. The residue obtained was purified by silica gel chromatography to give 2 (390 mg, 82%) as a white solid: mp 175°-176° C.; [α]D20 +44.0° (c 1.0, acetone); 1H NMR (CDCl3): δ 1.00 (t, 3H, J=7.30 Hz, --CH2CH3), 1.10 (d, 3H, J=6.9 Hz, --CH3), 1.40 (d, 3H, J=6.3 Hz, --CH3), 1.45, 1.47 (2s, 6H, --C(CH3)2), 1.62 (m, 2H, --CH2CH3), 1.71 (m, 1H, H-11), 2.86 (m, 2H, H-13), 2.91 (d, 1H, J=3.9 Hz, --OH), 4.24 (m, 1H, H-10), 4.94 (t, 1H, J=3.4 Hz, H-12), 5.50 (d, 1H, J=9.9 Hz, H-7), 5.90 (s, 1H, H-3), 6.61 (d, 1H, J=9.89 Hz, H-8); 13C NMR (CDCl3): δ 12.46, 13.94, 18.81, 23.20, 27.63, 27.81, 38.26, 38.51, 61.74, 72.94, 77.60, 103.47, 106.08, 106.39, 110.26, 116.55, 126.70, 151.33, 153.12, 153.90, 158.67, 160.95. Anal. Calcd for C22H26O5 : C, 71.33; H, 7.07. Found C, 71.18; H, 7.12.

Workup

  1. additionwas then added
  2. stirringstirring
  3. waitwas repeated after 2 h
  4. stirringthe reaction was stirred an additional 5 h
  5. customafter which time the solvent was evaporated
  6. customThe syrup obtained
  7. washwashed with water (30 mL)
  8. customThe aqueous layer was separated
  9. extractionextracted with EtOAc (2×30 mL)
  10. dry with materialThe combined organic layers were dried (MgSO4)
  11. concentrationconcentrated
  12. customThe residue obtained
  13. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-e8c339308e5e40f9bd64ab4da7ea7e61
Source dataset
uspto-grants-1997_03
Patent number
US05608085

Reaction notes

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