Iodoethane → 6'-bromo-4-ethoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one

6′-Bromo-4-hydroxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one as a 2:1 mixture of isomers (Intermediate 5 Step 2, 10.4 g, 34.1 mmol) and ethyl iodide (3.6 mL, 44.3 mmol) were dissolved in 2-MeTHF (100 mL) under N2. KOt-Bu (7.65 g, 68.2 mmol) was added portionwise to the reaction mixture, keeping the internal temperature below 30° C. The solution was stirred at r.t. overnight. Water (40 mL) and brine (25 mL) were added and the mixture was further stirred for min. The mixture was diluted with brine and 2-Me-THF until two layers formed. The phases were separated. Activated charcoal was added to the organic layer which was then stirred for 10 min. Diatomaceous earth was added and the mixture was further stirred for 5 min. The mixture was filtered through a plug of silica gel and diatomaceous earth, which was rinsed with heptane/EtOAc 7:3. The filtrate was concentrated. The filtration sequence was repeated, affording 4.0 g (36% yield) of the title compound (as a 2:1 mixture of isomers): 1H NMR (300 MHz, CDCl3) δ ppm 1.22 (t, 3 H), 1.32-1.45 (m, 2 H), 1.45-1.52 (m, 2 H), 1.77 (dt, 2 H), 2.07-2.16 (m, 2 H), 2.98 (s, 2 H), 3.30-3.40 (m, 1 H), 3.57 (q, 2 H), 7.34 (d, 1 H), 7.69 (dd, 1 H), 7.87 (d, 1 H).

1. customthe internal temperature below 30° C
2. stirringthe mixture was further stirred for min
3. customformed
4. customThe phases were separated
5. additionActivated charcoal was added to the organic layer which
6. stirringwas then stirred for 10 min
7. additionDiatomaceous earth was added
8. stirringthe mixture was further stirred for 5 min
9. filtrationThe mixture was filtered through a plug of silica gel and diatomaceous earth, which
10. washwas rinsed with heptane/EtOAc 7:3
11. concentrationThe filtrate was concentrated

ORD-Eintrag

ord-3195038cec8e4af985784ae452e752db

Quelldatensatz

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08865911B2