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

Temperature

0 °C

A mixture of isomers of 6′-bromo-4-hydroxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 5 Step 2, 12.7 g, 43.0 mmol) was dissolved in THF (210 mL) under N2 and cooled to 0° C. Potassium tert-butoxide (5.79 g, 51.6 mmol) was added portionwise and the mixture was stirred at 0° C. for 25 min. Methyl iodide (4.30 mL, 68.8 mmol) was added. The cooling bath was removed, and the mixture was stirred at r.t. Additional potassium tert-butoxide (0.483 g, 4.30 mmol) was added twice, after 2 h and 3 h respectively, and then the mixture was stirred for 2 h. Water (100 mL) was added and the resulting solution was partitioned between aq. NaCl solution (200 mL), and EtOAc (200 mL). The aq. phase was extracted with another portion of EtOAc (100 mL). The combined organic phases were dried (MgSO4) and evaporated to give 12.5 g (94% yield) of a mixture (approx. 80:20) of:

1. customThe cooling bath was removed
2. stirringthe mixture was stirred at r.t
3. stirringthe mixture was stirred for 2 h
4. customthe resulting solution was partitioned between aq. NaCl solution (200 mL), and EtOAc (200 mL)
5. extractionThe aq. phase was extracted with another portion of EtOAc (100 mL)
6. dry with materialThe combined organic phases were dried (MgSO4)
7. customevaporated

ORD record

ord-f1b4bb01eb1e42c190d2186f5b90d2af

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865911B2