Sodium hydride → ethyl (1R,2R)-2-(4-bromophenyl)cyclopropanecarboxylate

To a vigorously stirring mixture of (CH3)3S(I)O (7.76 g, 35.3 mmol) in DMSO (75 mL) was added NaH (0.972 g, 36.5 mmol) in small portions over 5 min. Following complete addition, the reaction was left to stir for 10 min before the rapid dropwise addition of ethyl trans-4-bromocinnamate (2.21 mL, 11.8 mmol), which is commercially available from, for example, Sigma-Aldrich. After 3 h the reaction was partitioned between EtOAc (100 mL) and H2O (200 mL). The aq. phase washed with EtOAc (2×75 mL) wherein the combined organics were washed with H2O (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting solid was absorbed onto Celite® and subjected to flash chromatography (SiO2—40 g; gradient elution: 5% EtOAc/Hexane isocratic for 3 min then 5-30% EtOAc/Hexane over 20 min at 40 mL/min to afford 1.48 g 13Ai as a white solid (46.7% yield). 1H NMR (500 MHz, CDCl3) δ 7.46-7.33 (m, 2H), 6.97 (d, J=8.6 Hz, 2H), 4.17 (q, J=7.2 Hz, 2H), 2.47 (ddd, J=9.2, 6.4, 4.3 Hz, 1H), 1.86 (ddd, J=8.5, 5.4, 4.2 Hz, 1H), 1.59 (dt, J=9.5, 4.8 Hz, 1H), 1.35-1.18 (m, 4H).

1. additionaddition
2. waitthe reaction was left
3. customAfter 3 h the reaction was partitioned between EtOAc (100 mL) and H2O (200 mL)
4. washThe aq. phase washed with EtOAc (2×75 mL) wherein the combined
5. washorganics were washed with H2O (2×50 mL), brine (50 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe resulting solid was absorbed onto Celite®
10. washgradient elution

ORD record

ord-f7c0581e75144dbeb64de540f42f15b0

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08063215B2