Methyl (2R)-2-oxiranecarboxylate → HCID 56955302, compound

Temperature

-10 °C

A solution of Li2CuCl4 (0.2 M in THF, 125 mL, 25.0 mmol) was added slowly to a suspension of cyclopentylmagnesium bromide (2 M in diethyl ether, 135 mL, 270 mmol; Aldrich Chemical Company, Inc., Milwaukee, Wis.) and THF (500 mL) at −50° C. over 2-3 mins. The pale grey/brown suspension was then allowed to warm slowly to −10° C. over 30 mins, by which time the color had developed to a dark grey. The mixture was re-cooled to −78° C. and (R)-methyl oxirane-2-carboxylate (25.0 g, 245 mmol; Aldrich Chemical Company, Inc., Milwaukee, Wis.) was added neat via syringe over 90 seconds. The reaction was then stirred at −78° C. for 20 mins, before removing the ice-bath and allowing to warm to approximately −50° C. over 30 mins. Saturated NH4Cl (aq, 700 mL) was then added and the mixture stirred for 30 mins. The organic layer was collected and the aqueous layer extracted with diethyl ether (2×250 mL). The combined organics were washed with saturated NH4Cl (aq, 350 mL), dried over MgSO4, and evaporated. Distillation of the crude residue (68-70° C. at 0.8 mbar) yielded 65-70% of (I-1b) as a pale yellow oil. A small amount of less volatile material remained in the still pot. 1H NMR (400 MHz; CDCl3): δ 4.17 (1 H), 3.76 (3 H), 2.67 (1 H), 2.01 (1 H), 1.48-1.88 (8 H), 1.11 (2 H).

1. temperatureThe mixture was re-cooled to −78° C.
2. custombefore removing the ice-bath
3. temperatureto warm to approximately −50° C. over 30 mins
4. additionSaturated NH4Cl (aq, 700 mL) was then added
5. stirringthe mixture stirred for 30 mins
6. customThe organic layer was collected
7. extractionthe aqueous layer extracted with diethyl ether (2×250 mL)
8. washThe combined organics were washed with saturated NH4Cl (aq, 350 mL)
9. dry with materialdried over MgSO4
10. customevaporated
11. distillationDistillation of the crude residue (68-70° C. at 0.8 mbar)
12. customyielded 65-70% of (I-1b) as a pale yellow oil

ORD record

ord-9665a9fe760b4031b89a93004642e3f0

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389552B2