Triethylamine → (2S)-2-[(1S)-5-methoxy-2,3-dihydro-1H-inden-1-yl]butanoic Acid

HRID 900524Notes

Reaction equation

HRID 900524 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C@H:12]([CH2:16][CH3:17])[C:13]([OH:15])=[O:14])=[CH:8][CH2:9]2)=[CH:5][CH:4]=1.C(N(CC)CC)C>CCO.C1COCC1>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6](=[CH:5][CH:4]=1)[C@H:7]([C@H:12]([CH2:16][CH3:17])[C:13]([OH:15])=[O:14])[CH2:8][CH2:9]2

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 11364955HCID 11364955, compound

Product 1

HCID 11345339(2S)-2-[(1S)-5-methoxy-2,3-dihydro-1H-inden-1-yl]butanoic AcidYield 95%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of the product obtained in Example 3 (105 g, 453 mmol), ClRh(PPh3)3 (21.0 g, 5% eq.) and triethylamine (68.8 g, 679.5 mmol) in EtOH (945 mL) and THF (105 mL) was shaken in a 2-L pressure bottle under 60 psi H2 for 16 hours. The solvents were removed at a reduced pressure. The resulting mixture was stirred in 1.5 L of 1N HCl solution and 1.5 L CH2Cl2. The aqueous layer was extracted with CH2Cl2 (2×250 mL). The combined CH2Cl2 layers were washed with 1 L of 1N HCl solution and stirred with 1 L of 1N NaOH solution. The organic layer was extracted with 1N NaOH solution (2×0.5 L). The combined aqueous layer was washed with CH2Cl2 (2×250 mL), and acidified (pH 2.0-3.0) by a slow addition of conc. HCl solution at below 15° C. The acidic mixture was extracted with CH2Cl2 (2×1.5 L), and washed with water (2×0.5 L) until pH 5.0-6.0. After washing with brine and drying over anhydrous Na2SO4, solvent was evaporated under a reduced pressure. The product (101.0 g, 95% yield, 96.8% ee) was obtained as a light yellow oil. 1H NMR (DMSO-d6) δ12.20(s, 1H), 7.04(d, 1H), 6.78(d, 1H), 6.66(dd, 1H), 3.70(s, 3H), 3.28(m, 1H), 2.72(m, 2H), 2.32(m, 1H), 2.06(m, 1H), 1.80(m, 1H), 1.50(m, 1H), 1.36(m, 1H), 0.82(t, 3H).

Workup

  1. customThe solvents were removed at a reduced pressure
  2. extractionThe aqueous layer was extracted with CH2Cl2 (2×250 mL)
  3. washThe combined CH2Cl2 layers were washed with 1 L of 1N HCl solution
  4. stirringstirred with 1 L of 1N NaOH solution
  5. extractionThe organic layer was extracted with 1N NaOH solution (2×0.5 L)
  6. washThe combined aqueous layer was washed with CH2Cl2 (2×250 mL)
  7. additionby a slow addition of conc. HCl solution at below 15° C
  8. extractionThe acidic mixture was extracted with CH2Cl2 (2×1.5 L)
  9. washwashed with water (2×0.5 L) until pH 5.0-6.0
  10. washAfter washing with brine
  11. dry with materialdrying over anhydrous Na2SO4, solvent
  12. customwas evaporated under a reduced pressure
  13. customThe product (101.0 g, 95% yield, 96.8% ee) was obtained as a light yellow oil

Sources & evidence

ORD record
ord-c6b4dde83ef94e10846359869eef50fd
Source dataset
uspto-grants-2008_04
Patent number
US07358386B2

Reaction notes

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