Boron trifluoride etherate → HCID 57889867, compound

Temperature

-78 °C

A 50 mL three neck round bottom flask equipped with a magnetic stirrer and two addition funnels, which had been flame dried under argon, charged with COPPER(I) CYANIDE (226 mg, 2.52 mmol), and evacuated under high vacuum overnight, was charged with THF (5 mL), and the suspension was cooled to −78° C. The mixture was treated with the dropwise addition of methyllithium (1.6 M in diethylether) (3.15 mL, 5.04 mmol). When the addition was complete, the cooling bath was removed, and the suspension was allowed to slowly warm, until a homogeneous solution was observed. The solution was cooled to −78° C., then treated with the slow dropwise addition of a solution of trans-benzyl 6-oxabicyclo[3.1.0]hexane-3-carboxylate (250 mg, 1.145 mmol) in THF (5 mL) followed by boron trifluoride etherate (0.581 mL, 4.58 mmol) in one portion. The mixture was stirred at −78° C. for 2 h, at which point a precipitate was observed, and the color quickly changed to bright yellow. The reaction was allowed to slowly come to room temperature, during which the color began to turn grey. The reaction was quenched with 30 mL of a 9:1 aqueous solution of saturated NH4Cl and 10% NH4OH, and the mixture was stirred for 30 minutes. The resulting deep blue mixture was filtered to remove a small amount of precipitate, and extracted 3× with ethyl acetate. The combined organic phases were washed with water followed by brine, then dried over sodium sulfate and concentrated in-vacuo. The residue was purified over a 2×15 cm silica gel column, eluting with ethyl acetate/hexanes (25%-50% EtOAc), to yield a racemic mixture of (1R,3R,4R)-benzyl 3-hydroxy-4-methylcyclopentanecarboxylate and (1S,3S,4S)-benzyl 3-hydroxy-4-methylcyclopentanecarboxylate (225 mg, 0.480 mmol, 84% yield) as a colorless oil.

1. additiontwo addition funnels, which
2. temperaturehad been flame
3. customdried under argon
4. customevacuated under high vacuum overnight
5. additionwas charged with THF (5 mL)
6. additionWhen the addition
7. customthe cooling bath was removed
8. temperatureto slowly warm, until a homogeneous solution
9. temperatureThe solution was cooled to −78° C.
10. customto slowly come to room temperature, during which
11. customThe reaction was quenched with 30 mL of a 9:1 aqueous solution of saturated NH4Cl and 10% NH4OH
12. stirringthe mixture was stirred for 30 minutes
13. filtrationThe resulting deep blue mixture was filtered
14. customto remove a small amount of precipitate
15. extractionextracted 3× with ethyl acetate
16. washThe combined organic phases were washed with water
17. dry with materialdried over sodium sulfate
18. concentrationconcentrated in-vacuo
19. customThe residue was purified over a 2×15 cm silica gel column
20. washeluting with ethyl acetate/hexanes (25%-50% EtOAc)
21. customto yield

ORD record

ord-a3bcb47a75df4f149277c912d6895619

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07601844B2