Hydrochloric Acid → HCID 14651533, compound

Temperature

-78 °C

To a 250 mL round-bottomed flask equipped with a stirbar and purged with nitrogen, was added 30 mL anhydrous THF followed by DIPA (2.21 g, 3.5 eq, 21.85 mmol). The mixture was cooled to −78° C. with stirring, n-BuLi (2.5 M, 3.3 eq, Aldrich) was then added dropwise, and the reaction was stirred for 10 min. To the flask was slowly added (R)-5-methoxy-3-methyl-5-oxopentanoic acid (1 g, 6.25 mmol, in 10.0 mL THF, Sumitomo) over about 2 min. After 30 min stirring at −78° C., a solution of methyl chloroformate (2.1 eq, 13.13 mmol) in THF (10 mL) was slowly added to the mixture. After the addition was complete, the reaction mixture was allowed warm to room temperature overnight. The reaction mixture was adjusted to about pH 5 to 6 (using pH paper), with cooling to maintain about ambient temperature using 2N aq. HCl. The reaction mixture was concentrated under reduced pressure, diluted with 75 mL EtOAc and 25 mL aq. 1N HCl. The layers were separated and the aqueous phase was extracted (2×15 mL EtOAc). The combined organics were washed with saturated aqueous NaCl (1×15 mL), dried over MgSO4, and concentrated under reduced pressure to give the product (1.36 g), which was used in the subsequent step without purification.

1. customTo a 250 mL round-bottomed flask equipped with a stirbar
2. custompurged with nitrogen
3. additionwas added 30 mL anhydrous THF
4. stirringthe reaction was stirred for 10 min
5. customover about 2 min
6. stirringAfter 30 min stirring at −78° C.
7. additionAfter the addition
8. temperaturethe reaction mixture was allowed warm to room temperature overnight
9. temperaturewith cooling
10. temperatureto maintain about ambient temperature
11. concentrationThe reaction mixture was concentrated under reduced pressure
12. additiondiluted with 75 mL EtOAc and 25 mL aq. 1N HCl
13. customThe layers were separated
14. extractionthe aqueous phase was extracted (2×15 mL EtOAc)
15. washThe combined organics were washed with saturated aqueous NaCl (1×15 mL)
16. dry with materialdried over MgSO4
17. concentrationconcentrated under reduced pressure

ORD record

ord-b513172df1ee4e90b66f2f005d613b8f

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309204B2