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

A solution of the product obtained in Example 18 (105 g, 453 mmol), ClRh(PPh3)3 (21.0 g, 22.7 mmol), and Et3N (68.8 g, 679.5 mmol) in EtOH (945 mL) and THF (105 mL) was shaken in a 2-L pressure bottle under H2 (60 psi) for 16 h. The solvents were removed under reduced pressure and the residue was taken up in a mixture of HCl (1.5 L, 1 N aqueous solution) and CH2Cl2 (1.5 L) and stirred. The aqueous layer was extracted with CH2Cl2 (2×250 mL). The combined organic layers were washed with HCl (1 L, 1 N aqueous solution) and stirred with NaOH (1 L, 1 N aqueous solution). The organic layer was extracted with NaOH (2×0.5 L, 1 N aqueous solution). The combined aqueous layer was washed with CH2Cl2 (2×250 mL), and acidified (pH 2.0-3.0) by a slow addition of HCl (37% aqueous solution) maintaining the temperature below 15° C. The acidic-mixture was extracted with CH2Cl2 (2×1.5 L). The combined organic phases were washed with water (2×0.5 L) until pH 5.0-6.0 and brine, dried over Na2SO4, filtered, and then concentrated under reduced pressure. The product (101.0 g, 95% yield, 96.8% ee) was obtained as a light yellow oil. The absolute configuration of the title compound was determined by single crystal x-ray crystallography of the corresponding (R)-(+)-methyl benzylamine salt. 1H NMR (300 MHz), (DMSO-d6) δ 12.20 (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).

1. customThe solvents were removed under reduced pressure
2. additionthe residue was taken up in a mixture of HCl (1.5 L, 1 N aqueous solution) and CH2Cl2 (1.5 L)
3. extractionThe aqueous layer was extracted with CH2Cl2 (2×250 mL)
4. washThe combined organic layers were washed with HCl (1 L, 1 N aqueous solution)
5. stirringstirred with NaOH (1 L, 1 N aqueous solution)
6. extractionThe organic layer was extracted with NaOH (2×0.5 L, 1 N aqueous solution)
7. washThe combined aqueous layer was washed with CH2Cl2 (2×250 mL)
8. additionby a slow addition of HCl (37% aqueous solution)
9. temperaturemaintaining the temperature below 15° C
10. extractionThe acidic-mixture was extracted with CH2Cl2 (2×1.5 L)
11. washThe combined organic phases were washed with water (2×0.5 L) until pH 5.0-6.0 and brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe product (101.0 g, 95% yield, 96.8% ee) was obtained as a light yellow oil

ORD record

ord-c7497ef471444b1a9edb00bbc63e79aa

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07476742B2