Triethylamine → HCID 69622946, compound

Temperature

0 °C

To a mechanically stirred solution of 9.50 g (83.2 mmol, 1.10 equiv.) of 4-hexenoic acid (commericially available from Lancaster, Catalog #252-427-6) and 13.9 mL (10.1 g, 99.7 mmol, 1.33 equiv.) of triethylamine in 150 mL of dry THF, cooled to −78° C. under dry N2, was added 10.71 mL (10.49 g, 87.0 mmol, 1.15 equiv.) of pivaloyl chloride (Aldrich). The mixture was warmed to 0° C. for 60 min, and then recooled to −78° C. A solution of 13.4 g (75.6 mmol, 1.00 equiv) of (S)-(−)-(phenylmethyl)-2-oxazolidone (Aldrich) and 22 mg of triphenylmethane (indicator) in 150 mL of dry THF, stirred at −30° C. to −45° C. under N2, was treated dropwise with n-butyllithium (−2.5 M in hexanes) (Aldrich) until an orange color persisted (−30 mL required). The resulting solution was cooled to −78° C. and then added, via rapid cannulation, to the above stirred mixture containing the mixed anhydride. The residual lithiated oxazolidone was rinsed in with two 10-mL portions of dry THF and the resulting mixture was stirred at −78° C. for 1.5 h, and then at 0° C. for 1 h. The mixture was partitioned between CH2Cl2 and pH 7 phosphate buffer. The CH2Cl2 phase was washed with saturated aqueous NaHCO3 followed by half-saturated aqueous NaCl, dried (MgSO4), and evaporated in vacuo. The residual cream-colored solid (22.4 g) was chromatographed (Waters Prep 2000, 5.0 cm×25 cm 10μ Kromasil KR60-1OSIL-5025 column) in two batches eluting with 85:15 hexanes/EtOAc. The chromatographed product was recrystallized from hexane to yield 14.34 g (first crop, 69%) of the title compound as fine white needles. 1H NMR (300 MHz, CDCl3) δ7.37-7.20 (m, 5H, —C6H5), 5.60-5.43(m, 2H, CH═CHCH3), 4.71-4.63 (m, 1H, NCH(Ph) CH2O), 4.23-4.14 (m, 2H, NCH(Ph)CH2O), 3.295 (dd, J=13.3, 3.3 Hz, 1H, CHHC6H5), 3.11-2.90 (m, 2H, CH2C═O), 2.758 (dd, J=13.3, 9.6 Hz, 1H, CHHC6H5), 2.42-2.34 (m, 2H, CH═CHCH2), 1.67-1.65 (m, 2H, CH═CHCH3).

1. customrecooled to −78° C
2. temperatureThe resulting solution was cooled to −78° C.
3. additionadded, via rapid cannulation, to the above stirred mixture
4. washThe residual lithiated oxazolidone was rinsed in with two 10-mL portions of dry THF
5. waitat 0° C. for 1 h
6. customThe mixture was partitioned between CH2Cl2 and pH 7 phosphate buffer
7. washThe CH2Cl2 phase was washed with saturated aqueous NaHCO3
8. dry with materialdried (MgSO4)
9. customevaporated in vacuo
10. customThe residual cream-colored solid (22.4 g) was chromatographed (Waters Prep 2000, 5.0 cm×25 cm 10μ Kromasil KR60-1OSIL-5025 column) in two batches
11. washeluting with 85:15 hexanes/EtOAc
12. customThe chromatographed product was recrystallized from hexane

ORD record

ord-61147334b00f4f7bb37a4fce0b522a76

Source dataset

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06191166B1