Reaction #1857565

Reaction equation

(2S,3S,4S,8S)-3-butyl-8-(3-hydroxy-4-methoxypicolinamido)-2-methyl-9-oxooxonan-4-ylisobutyrate

Na2CO3

NaI

chloromethyl 2-ethoxyacetate

acetone

→

title compound

Yield 41.0%

(2S,3S,4S,8S)-3-butyl-8-(3-((2-ethoxyacetoxyl)methoxy)-4-methoxypicolinamido)-2-methyl-9-oxooxonan-4-yl isobutyrate

Yield 41.0%

Conditions

Workup

1. 1
   OtherThe sealed reaction
2. 2
   TemperatureThe reaction was cooled to room temperature
3. 3
   Concentrationconcentrated under a stream of N2
4. 4
   OtherThe resulting residue was purified by flash column chromatography (4 g SiO2, 0→100% EtOAc/hexanes)

Procedure

To a solution of (2S,3S,4S,8S)-3-butyl-8-(3-hydroxy-4-methoxypicolinamido)-2-methyl-9-oxooxonan-4-ylisobutyrate (45 mg, 0.097 mmol), Na2CO3 (20.5 mg, 0.194 mmol), and NaI (22.2 mg, 0.145 mmol) in acetone (2.0 mL) was added chloromethyl 2-ethoxyacetate (22.2 mg, 0.145 mmol). The sealed reaction was warmed to 45° C. and stirred for 16 h. The reaction was cooled to room temperature and concentrated under a stream of N2. The resulting residue was purified by flash column chromatography (4 g SiO2, 0→100% EtOAc/hexanes) to afford the title compound (23.2 mg, 0.040 mmol, 41%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J=8.1 Hz, 1H), 8.28 (d, J=5.4 Hz, 1H), 6.95 (d, J=5.4 Hz, 1H), 5.82 (s, 2H), 4.90 (ddd, J=9.1, 5.6, 1.9 Hz, 1H), 4.83 (dq, J=10.0, 6.4 Hz, 1H), 4.62 (ddd, J=10.7, 8.1, 7.1 Hz, 1H), 4.10 (s, 2H), 3.90 (s, 3H), 3.59 (q, J=7.0 Hz, 2H), 2.53 (hept, J=7.0 Hz, 1H), 2.36 (dt, J=13.7, 6.8 Hz, 1H), 2.21-2.03 (m, 2H), 1.87-1.76 (m, 1H), 1.60-1.51 (m, 1H), 1.41-1.32 (m, 5H), 1.32-1.25 (m, 3H), 1.23 (t, J=7.0 Hz, 4H), 1.17 (dd, J=7.0, 0.8 Hz, 7H), 1.05 (ddt, J=15.9, 7.5, 2.2 Hz, 1H), 0.88 (t, J=7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 176.48, 172.33, 170.05, 162.94, 160.18, 145.80, 143.89, 142.32, 109.69, 89.56, 74.52, 73.29, 67.80, 67.19, 56.22, 51.32, 45.49, 34.29, 32.91, 30.88, 28.17, 27.45, 23.30, 19.22, 19.09, 18.94, 18.14, 15.01, 13.88; HRMS-ESI m/z [M+H]+ calcd for: C29H44N2O10, 581.3069; found 581.3073.

Source