Trifluoroacetic acid → (+)-12-Oxocalanolide A

HRID 1637977

Reaction equation

HRID 1637977 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-81e9fda0000d46f78da64495f4fb30d8
Source dataset
uspto-grants-2000_03
Patent number
US06043271

Linked notes

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