Trimethyl orthoformate → Ethyl 4,4-dimethoxycyclohexane-1-carboxylate

To a solution of ethyl-4-oxocyclohexane carboxylate (23.4 mL, 147 mmol) and p-TsOH (0.25 g, 1.31 mmol) in 25 mL MeOH was added HC(OMe)3 (24.10 mL, 220 mmol) dropwise. The reaction was stirred at rt for 15 h and 1.5 g of anhydrous Na2CO3 was added. The reaction was stirred at rt for another 30 min and filtered. TEA (0.18 mL, 1.31 mmol) was added to the filtrate and the resulting mixture was concentrated in vacuo. The residue was diluted with EtOAc (30 mL), washed with water (4×30 mL), dried (MgSO4), filtered, and concentrated in vacuo. The crude oil was purified by flash chromatography on SiO2 (0 to 20% EtOAc:hexanes) to afford the title compound (32 g, 100% yield) as a clear oil. 1H NMR (500 MHz, CDCl3) δ 4.15 (q, J=7.1 Hz, 2H), 3.21 (s, 3H), 3.18 (s, 3H), 2.41-2.28 (m, 1H), 2.08-1.96 (m, 2H), 1.91-1.79 (m, 2H), 1.77-1.61 (m, 2H), 1.43 (td, J=12.9, 4.1 Hz, 2H), 1.27 (t, J=7.1 Hz, 3H).

1. stirringThe reaction was stirred at rt for another 30 min
2. filtrationfiltered
3. concentrationthe resulting mixture was concentrated in vacuo
4. additionThe residue was diluted with EtOAc (30 mL)
5. washwashed with water (4×30 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude oil was purified by flash chromatography on SiO2 (0 to 20% EtOAc:hexanes)

ORD record

ord-e675a1e63d944b18b681fed9d511fa09

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962660B2