Sulfuric Acid → (R)-methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetate

HRID 1848772Notes

Reaction equation

HRID 1848772 reaction equation
N[C@H:2](C)C(C1C=CC=CC=1)(C1C=CC=CC=1)O.[OH:18][C:19]1[CH:31]=[CH:30][C:22]2[C@@H:23]([CH2:26][C:27]([OH:29])=[O:28])[CH2:24][O:25][C:21]=2[CH:20]=1.S(=O)(=O)(O)O>CO>[OH:18][C:19]1[CH:31]=[CH:30][C:22]2[C@@H:23]([CH2:26][C:27]([O:29][CH3:2])=[O:28])[CH2:24][O:25][C:21]=2[CH:20]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 86706789HCID 86706789, compound

Product 1

HCID 67812739(R)-methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetateYield 91.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

[(3R)-6-Hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetic acid (R)-2-amino-1,1-diphenylpropan-1-ol salt (100 g) and sulfuric acid (30.26 g) were added to methanol (120 mL), and the mixture was stirred at 60° C. for 2 hr. After allowing to cool to room temperature, the solvent was concentrated under reduced pressure. To the residue were added toluene (831 mL), tetrahydrofuran (415 mL) and 1M hydrochloric acid (500 mL), and the mixture was partitioned. The organic layer was washed with water (500 mL), 5% aqueous sodium hydrogen carbonate solution (500 mL) and water (500 mL). The organic layer was concentrated, and toluene (110 mL) was added to the residue. The mixture was heated to 50° C., dissolved, allowed to cool to room temperature, and solid precipitation was confirmed. Normal heptane (220 mL) was added, and the mixture was stirred at room temperature for 5 hr. After cooling to 5° C., the solid was collected by filtration, washed with a mixed solution (1:2, 24 mL) of toluene-normal heptane. The solid was dried at 50° C. under reduced pressure to give the title compound (45.19 g). 99.6% ee.

Workup

  1. temperatureto cool to room temperature
  2. concentrationthe solvent was concentrated under reduced pressure
  3. additionTo the residue were added toluene (831 mL), tetrahydrofuran (415 mL) and 1M hydrochloric acid (500 mL)
  4. customthe mixture was partitioned
  5. washThe organic layer was washed with water (500 mL), 5% aqueous sodium hydrogen carbonate solution (500 mL) and water (500 mL)
  6. concentrationThe organic layer was concentrated
  7. additiontoluene (110 mL) was added to the residue
  8. temperatureThe mixture was heated to 50° C.
  9. dissolutiondissolved
  10. temperatureto cool to room temperature
  11. customsolid precipitation
  12. additionNormal heptane (220 mL) was added
  13. stirringthe mixture was stirred at room temperature for 5 hr
  14. temperatureAfter cooling to 5° C.
  15. filtrationthe solid was collected by filtration
  16. washwashed with a mixed solution (1:2, 24 mL) of toluene-normal heptane
  17. customThe solid was dried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-a7386cbcb4384c6dbfd58680ff30a9fc
Source dataset
uspto-grants-2015_02
Patent number
US08952185B2

Reaction notes

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