HCID 54064141, compound → HCID 59656743, compound

Temperature

0 °C

tert-butyl 3-(tert-butyldimethylsilyloxy)-1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamate (22a) (1.5 g, 4.0 mmol, 1.0 equiv.) was added to a 100 mL RBF followed by THF (33 mL). The mixture was cooled to 0° C. via an ice bath and a 1.0 M solution of EtMgBr in THF (12.0 mL, 12.0 mmol, 3.0 equiv.) was added over 10 min. The reaction stirred for 30 min at 0° C. and the ice bath was removed. The reaction stirred for an additional 1.0 h at rt. and was again cooled to 0° C. via an ice bath. Next, the reaction was quenched by addition of 1.0 M HCl (33 mL). The solution was transferred to a separatory funnel with additional 1.0 M HCl (20 mL) and extracted with EtOAc (3×40 mL). The organic layers were washed with sat. NaCl (2×30 mL) and dried over Na2SO4. The solution was then concentrated on a rotary evaporator and dried under vacuum to give 1.4 g of crude material. The residue was purified by flash column chromatography (10% EtOAc/hexanes) to give 1.1 g (86%) of 26 as a clear oil. Rf=0.25 (10% EtOAc/hexanes); IR (film) 3431, 3371, 2975, 2953, 2930, 2883, 2856, 1711, 1492, 1172, 838 cm−1; 1H NMR (500 MHz, CDCl3) δ 5.45 (d, J=7.0 Hz, 1H, carbamate-NH), 4.22 (m, 1H, Boc-NH—CH), 4.00 (dd, J=10.0, 3.5 Hz, 1H, CH—CH2), 3.76 (dd, J=10.0, 4.0 Hz, 1H, CH—CH2), 2.56 (m, 1H, O═C—CH2), 2.44 (m, 1H, O═C—CH2), 1.39 (s, 9H, Boc-tbutyl-CH3), 1.08 (t, J=7.0 Hz, 3H, O═C—CH2CH3), 0.79 (s, 9H, Si-t-butyl-CH3), −0.03 (s, 6H, Si—CH3); 13C NMR (125 MHz, CDCl3) δ 208.5, 155.5, 79.7, 63.6, 61.2, 33.5, 28.4, 25.8, 18.2, 7.5, −5.5, −5.5; LRMS (ESI-MS m/z): Mass calcd for C16H33NO4Si [M]+, 331.52. Found 332.

1. customthe ice bath was removed
2. stirringThe reaction stirred for an additional 1.0 h at rt
3. temperatureand was again cooled to 0° C. via an ice bath
4. customNext, the reaction was quenched by addition of 1.0 M HCl (33 mL)
5. customThe solution was transferred to a separatory funnel with additional 1.0 M HCl (20 mL)
6. extractionextracted with EtOAc (3×40 mL)
7. washThe organic layers were washed with sat. NaCl (2×30 mL)
8. dry with materialdried over Na2SO4
9. concentrationThe solution was then concentrated on a rotary evaporator
10. customdried under vacuum
11. customto give 1.4 g of crude material
12. customThe residue was purified by flash column chromatography (10% EtOAc/hexanes)

ORD record

ord-585424f582034a12b036a722be43908c

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07829304B2