tert-Butanol → Ethyl 1-[[(1,1-dimethylethoxy)carbonyl]amino]-3,3-difluorocyclobutanecarboxylate
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1(C(O)=O)[CH2:9][C:8]([F:11])([F:10])[CH2:7]1)=[O:5])[CH3:2].[C:15]([OH:19])([CH3:18])([CH3:17])[CH3:16].C1C=CC(P([N:34]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.C([O:40][CH2:41]C)(=O)C>O1CCOCC1>[C:15]([O:19][C:41]([NH:34][C:6]1([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][C:8]([F:10])([F:11])[CH2:9]1)=[O:40])([CH3:18])([CH3:17])[CH3:16]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 1-(ethoxycarbonyl)-3,3-difluorocyclobutanecarboxylic acid (162) (1 g, 4.8 mmol) in dry dioxane (18 mL) was added tert-butanol (0.4 mL, 4.3 mmol), DPPA (1.03 mL, 4.8 mmol) and TEA (0.7 mL, 4.9 mmol) and the mixture was refluxed overnight. Ethyl acetate was added and the organic layer was washed twice with 5% citric acid and saturated sodium hydrogen carbonate. The solution was dried and evaporated under reduced pressure. The product was purified using silica gel chromatography using hexanes/ethyl acetate to yield ethyl 1-((tert-butoxycarbonyl)amino)-3,3-difluorocyclobutanecarboxylate (163). 1H NMR (400 MHz, CD2Cl2) δ 4.12 (q, J=6.8 Hz, 2H), 3.18-3.08 (m, 2H), 2.73-2.55 (m, 2H), 1.34 (s, 9H), 1.19 (t, J=6.8 Hz, 4H). MS m/z 280.1 (M+1)+.
Workup
- temperaturethe mixture was refluxed overnight
- washthe organic layer was washed twice with 5% citric acid and saturated sodium hydrogen carbonate
- customThe solution was dried
- customevaporated under reduced pressure
- customThe product was purified
Sources & evidence
- ORD record
- ord-1ec7563febcd4ddfba16a5f0cc5ae487
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09199981B2
Reaction notes
Loading…