Trifluoroacetic acid → (+)-12-Oxocalanolide A

HRID 362224

Reaction equation

HRID 362224 reaction equation
[CH3:1][C:2]1([CH3:25])[O:7][C:6]2[C:8]3[C:13]([CH2:14][CH2:15][CH3:16])=CC(=O)O[C:9]=3[C:18]([C:21](=[O:24])[CH2:22][CH3:23])=[C:19]([OH:20])[C:5]=2[CH:4]=[CH:3]1.[CH2:26](OC(OCC)C)[CH3:27].F[C:35](F)(F)[C:36]([OH:38])=[O:37]>C(OCC)(=O)C>[CH3:16][CH2:15][CH2:14][C:13]1[C:8]2[C:6]3[O:7][C:2]([CH3:1])([CH3:25])[CH:3]=[CH:4][C:5]=3[C:19]3[O:20][C@H:26]([CH3:27])[C@@H:22]([CH3:23])[C:21](=[O:24])[C:18]=3[C:9]=2[O:38][C:36](=[O:37])[CH:35]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7765AcetalHCID 54948815-Hydroxy-2,2-dimethyl-6-propionyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one

Product 1

HCID 463613(+)-12-Oxocalanolide AYield 30%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A solution containing chromene 4 (344 mg, 1.0 mmol), acetaldehyde diethylacetal (473 mg, 4.0 mmol), trifluoroacetic acid (1.5 mL, 19.4 mmol) and anhydrous pryidine (0.7 mL) was heated at 140° C. under N2. The reaction was monitored by TLC analysis. After 4 hours, the reaction mixture was cooled to room temperature, diluted with ehtyl acetate and washed several times with 10% aqueous NaHCO3 and brine. The organic layer was separated and dried over Na2SO4. The solvent was removed in vacuo and the crude product was purified by silica gel column chromatography eluting with ethyl acetate/hexane (2:3). Chromanone 7 (10,11-trans-dihydro-6,6,10,11-tetramethyl-4-propyl-2H,6H,12H-benzo[1,2-b:3,4-b':5,6-b"]-tripyran-2,12-dione) (110 mg, 30% yield) was obtained m.p. 176°~177° C. (Lit.5 130°~132° C.). 1H-NMR5 (CDCl3) δ 1.02 (3H, t, J=7.5 Hz, CH3); 1.21 (3H, d, J=6.8 Hz, CH3); 1.51 (3H, d, J=7.0 Hz, CH3); 1.55 (6H, 2s, 2 CH3); 1.63 (2H, sextet, J=7.0 Hz, CH2); 2.55 (1H, dq, J=6.9 Hz, J=11.0 Hz, H11); 2.88 (2H, t, J=7.6 Hz, CH2); 4.28 (1H, dq, J=6.3 Hz, J=11.0 Hz, H10); 5.60 (1H, d, J=9.9 Hz, H8); 6.04 (1H, s, H3); 6.65 (1H, d, J=11.8 Hz, H7); MS (CI): 369 (100, M+1).

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. washwashed several times with 10% aqueous NaHCO3 and brine
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed in vacuo
  6. customthe crude product was purified by silica gel column chromatography
  7. washeluting with ethyl acetate/hexane (2:3)

Sources & evidence

ORD record
ord-3c7c6b58bee14bd8a469e50ff9125d90
Source dataset
uspto-grants-1999_02
Patent number
US05869324

Linked notes

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