Acetic Acid → 8-Isopropyl-2,2,4,4-tetramethyl-chroman-6-carboxylic acid 4-(2-carboxy-vinyl)-phenyl ester

HRID 1765742Notes

Reaction equation

HRID 1765742 reaction equation
C([SiH](C)C)(C)(C)C.C(N(CC)CC)C.C([O:22][C:23]([CH:25]=[CH:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][C:34]([C:36]2[CH:37]=[C:38]3[C:43](=[C:44]([CH:46]([CH3:48])[CH3:47])[CH:45]=2)[O:42][C:41]([CH3:50])([CH3:49])[CH2:40][C:39]3([CH3:52])[CH3:51])=[O:35])=[CH:29][CH:28]=1)=[O:24])C1C=CC=CC=1.C(O)(=O)C>ClCCl.O.O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:23]([CH:25]=[CH:26][C:27]1[CH:28]=[CH:29][C:30]([O:33][C:34]([C:36]2[CH:37]=[C:38]3[C:43](=[C:44]([CH:46]([CH3:47])[CH3:48])[CH:45]=2)[O:42][C:41]([CH3:50])([CH3:49])[CH2:40][C:39]3([CH3:51])[CH3:52])=[O:35])=[CH:31][CH:32]=1)([OH:24])=[O:22]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5072427tert-ButyldimethylsilaneHCID 690737328-Isopropyl-2,2,4,4-tetramethyl-chroman-6-carboxylic acid 4-(2-benzyloxycarbonyl-vinyl)-phenyl ester2×

Product 1

HCID 690714768-Isopropyl-2,2,4,4-tetramethyl-chroman-6-carboxylic acid 4-(2-carboxy-vinyl)-phenyl esterYield 13.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of t-butyldimethyl silane (0.3 mL, 1.85 mmol), palladium(II)acetate (0.013 g, 0.06 mmol) and triethyl amine (0.03 mL, 0.2 mmol) in anhydrous dichloromethane (2 mL) under argon was treated with a solution of 8-isopropyl-2,2,4,4-tetramethyl-chroman-6-carboxylic acid 4 (2-benzyloxycarbonyl-vinyl)-phenyl ester (Intermediate 35, 0.063 g, 0.123 mmol) in dichloromethane (2 mL) and the resulting reaction mixture was stirred overnight at ambient temperature. The reaction mixture was quenched with water and extracted with diethyl ether. The organic extract was dried over anhydrous sodium sulfate, filtered and evaporated to a residue that was subjected to flash column chromatography to yield an intermediate that was treated with acetic acid (1 mL) in water (0.3 mL) and tetrahydrofuran (0.3 mL) at ambient temperature for 1 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was dried over anhydrous sodium sulfate, filtered and evaporated to a residue that was subjected to preparative reverse phase HPLC using 10% water in acetonitrile as the mobile phase to afford the title compound (0.007 g).

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with diethyl ether
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated to a residue that
  8. customto yield an intermediate
  9. extractionextracted with ethyl acetate
  10. extractionThe organic extract
  11. dry with materialwas dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customevaporated to a residue that

Sources & evidence

ORD record
ord-4aad76158a4b45f5a093df806a6b1e95
Source dataset
uspto-grants-2007_06
Patent number
US07226951B2

Reaction notes

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