Lithium Hydroxide → 2-(4-Bromophenyl)cyclopropanecarboxylic acid

温度

50 °C

In a round bottom flask, mixed the tert-butyl 2-(4-bromophenyl)cyclopropanecarboxylate 2 (3.7 g, 12.0 mmol) in methanol/tetrahydrofuran (1:1, 30 mL) and heated to 50° C. Separately dissolved lithium hydroxide (1.4 g, 60 mmol) in water (15 mL) and then added to the solution of 2. Increased the heat to 65° C., and monitored by HPLC for reaction completion (<1% pA of 2, ˜3 h). The reaction mixture was then cooled to room temperature and distilled to ½ volume. Cooled the suspension to <20° C. and acidified (exothermic addition) the product mixture to pH<2 with 2N HCl (˜30 mL) to precipitate the product. Stirred the resulting suspension at 20° C. for NLT 0.5 h. Filtered the suspension and washed the wetcake with water (˜20 mL). Dried the wetcake at 45° C. under vacuum. Isolated 2.96 g of an off-white solid (98% pA, 97 wt %=99% wt-adjusted yield). 1H NMR (400 MHz, CDCl3) δ 1.35-1.40 (m, 1H), 1.65-1.69 (m, 1H), 1.85-1.89 (m, 1H), 2.53-2.58 (m, 1H), 6.97 (d, 2H, J=8.37), 7.40 (d, 2H, J=8.37). 13C NMR (100 MHz, CDCl3) δ 17.7, 24.2, 26.7, 120.2, 127.7, 131.3, 138.1 & 178.9 with 2 peaks overlapping.

1. temperatureIncreased the
2. temperatureheat to 65° C.
3. custommonitored by HPLC for reaction completion (<1% pA of 2, ˜3 h)
4. temperatureThe reaction mixture was then cooled to room temperature
5. distillationdistilled
6. temperatureCooled the suspension to <20° C.
7. addition(exothermic addition) the product mixture to pH<2 with 2N HCl (˜30 mL)
8. customto precipitate the product
9. filtrationFiltered the suspension
10. washwashed the wetcake with water (˜20 mL)
11. customDried the wetcake at 45° C. under vacuum

ORDレコード

ord-1a6ef0e87008463c8fb4c67e42bbf579

出典データセット

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08853390B2