Triethylamine → (1S,2S) 2-Ethyl-1-(2trimethylsilanylethoxycarbonylamino)cyclopropane-carboxylic acid tert-butyl ester

To a suspension of the product of Step 2 (10 g, 46.8 mmol) and 3 g of freshly activated 4 Å molecular sieves in dry benzene (160 mL) was added triethylamine (7.50 mL, 53.8 mmol) and DPPA (11 mL, 10.21 mmol). The reaction mixture was heated to reflux for 3.5 hours, treated with 2-trimethylsilyl-ethanol (13.5 mL, 94.2 mmol), and heated to reflux overnight. The reaction mixture was filtered, diluted with diethyl ether, washed sequentially with 10% aqueous citric acid solution, water, saturated aqueous NaHCO3, water (2×), and brine (2×), dried (MgSO4), filtered, and concentrated in vacuo. The residue was suspended with 10 g of Aldrich polyisocyanate scavenger resin in 120 mL of dichloromethane, stirred at room temperature overnight, and filtered to provide the desired product (8 g, 24.3 mmol; 52%) as a pale yellow oil: 1H NMR (CDCl3) δ 0.03 (s, 9H), 0.97 (m, 5H), 1.20 (br m, 1H), 1.45 (s, 9H), 1.40-1.70 (m, 4H), 4.16 (m, 2H), 5.30 (br s, 1H).

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 3.5 hours
3. temperatureheated
4. temperatureto reflux overnight
5. filtrationThe reaction mixture was filtered
6. additiondiluted with diethyl ether
7. washwashed sequentially with 10% aqueous citric acid solution, water, saturated aqueous NaHCO3, water (2×), and brine (2×)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. filtrationfiltered

ORD record

ord-d2df0d12186b471195c2fd8df180f65f

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07935670B2