Sulfuric Acid → (S)-Methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetate

HRID 1848768Notes

Reaction equation

HRID 1848768 reaction equation
[C:1]1([C@H](N)C)C=CC=CC=1.[OH:10][C:11]1[CH:23]=[CH:22][C:14]2[C@H:15]([CH2:18][C:19]([OH:21])=[O:20])[CH2:16][O:17][C:13]=2[CH:12]=1.S(=O)(=O)(O)O.CCCCCCC>CO.C1(C)C=CC=CC=1>[OH:10][C:11]1[CH:23]=[CH:22][C:14]2[C@H:15]([CH2:18][C:19]([O:21][CH3:1])=[O:20])[CH2:16][O:17][C:13]=2[CH:12]=1

Participants

6

Reactant 3

HCID 1118Sulfuric AcidHCID 8900HeptaneHCID 60164156HCID 60164156, compound

Product 1

HCID 53393313(S)-Methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetateYield 83.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of [(3S)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetic acid (1R)-1-phenylethylamine salt (1.0 g) in methanol (3 mL)-toluene (8 mL) was added concentrated sulfuric acid (0.412 mg), and the mixture was stirred at 60° C. for 2 hr. The mixture was concentrated, toluene (5 mL) was added, and the mixture was concentrated again. To the residue were added toluene (5 mL), tetrahydrofuran (8 mL) and 1N hydrochloric acid (5 mL) to perform an extraction operation. The organic layer was washed with water, 5% aqueous sodium bicarbonate and water, and concentrated, and the residue was dissolved in toluene (8 mL). The activated carbon (100 mg) was added, and the mixture was stirred at room temperature for 30 min. After filtration, the filtrate was concentrated. The obtained crude product was dissolved in toluene (2 mL), seed crystal was added, and the mixture was stirred at room temperature for 16 hr. n-Heptane (6 mL) was added, and the mixture was stirred at room temperature for 5 hr and at 0° C. for 1 hr. The precipitated crystals were collected by filtration, and dried at 50° C. to give the title compound (554 mg) as white crystals. 99.7% ee.

Workup

  1. concentrationThe mixture was concentrated
  2. additiontoluene (5 mL) was added
  3. concentrationthe mixture was concentrated again
  4. additionTo the residue were added toluene (5 mL), tetrahydrofuran (8 mL) and 1N hydrochloric acid (5 mL)
  5. washThe organic layer was washed with water, 5% aqueous sodium bicarbonate and water
  6. concentrationconcentrated
  7. dissolutionthe residue was dissolved in toluene (8 mL)
  8. additionThe activated carbon (100 mg) was added
  9. stirringthe mixture was stirred at room temperature for 30 min
  10. filtrationAfter filtration
  11. concentrationthe filtrate was concentrated
  12. customThe obtained crude product
  13. additionseed crystal was added
  14. stirringthe mixture was stirred at room temperature for 16 hr
  15. stirringthe mixture was stirred at room temperature for 5 hr and at 0° C. for 1 hr
  16. filtrationThe precipitated crystals were collected by filtration
  17. customdried at 50° C.

Sources & evidence

ORD record
ord-9c313545cd824023a72f3028c10407f1
Source dataset
uspto-grants-2015_02
Patent number
US08952185B2

Reaction notes

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