Acetone cardice → ethyl 8-[hydroxy(phenyl)methyl]-6-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855062

Reaction equation

HRID 855062 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH3:22])[CH:6]=[C:7]2[C:12]=1[O:11][CH:10]([C:13]([F:16])([F:15])[F:14])[C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:8]2)=[O:2].C(=O)=O.CC(C)=O.[C:30]1([Mg]Br)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C1COCC1>[OH:2][CH:1]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:3]1[CH:4]=[C:5]([CH3:22])[CH:6]=[C:7]2[C:12]=1[O:11][CH:10]([C:13]([F:16])([F:14])[F:15])[C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:8]2

Participants

5

Reactant 3

HCID 18522661Acetone cardiceHCID 86599485ethyl 8-formyl-6-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylateHCID 178418255HCID 178418255, compound

Product 1

HCID 69517053ethyl 8-[hydroxy(phenyl)methyl]-6-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The ethyl 8-formyl-6-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylate prepared as in Example 605a, Step 1 (0.45 g, 1.43 mmole) was dissolved in anhydrous THF (5 mL) and the solution was cooled to −78° C. (dry ice/acetone). Phenylmagnesium bromide (1.58 mL, 1.58 mmole) was added to the above solution dropwise, which was allowed to stir for 4 hours. The reaction was quenched with saturated ammonium chloride (20 mL) and extracted with EtOAc (2×20 mL). The combined extracts were washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo to give an orange oil. The oil was purified by flash chromatography (silica gel) with 100% CH2Cl2 to give a light yellow oil (0.3g, 54%): GCMS m/z 392.0 (M+). 1H NMR (CDCl3/400 MHz) 7.62 (s, 1H), 7.32 (m, 6H), 6.95 (s, 1H), 6.10 (s, 1H), 5.68 (q, 1H, J=7.0 Hz), 4.28 (m, 2H), 2.28 (s, 3H), 1.32 (m, 3H).

Workup

  1. customThe reaction was quenched with saturated ammonium chloride (20 mL)
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined extracts were washed with brine (20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an orange oil
  8. customThe oil was purified by flash chromatography (silica gel) with 100% CH2Cl2

Sources & evidence

ORD record
ord-2ad4bc0f5a264434b47a153b6a480cc8
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Linked notes

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