Phosphorus trichloride → (4S)-2-bromobicyclo[2.2.1]heptane-1-carboxylic acid

To a 50 mL round-bottomed flask was added (1S,4R)-bicyclo[2.2.1]heptane-2-carboxylic acid (9.84 g, 70 mmol) and bromine (4.10 ml, 80 mmol). The suspension was stirred at room temperature until dissolution. Trichlorophosphine (0.30 ml, 3.4 mmol) was then added slowly and drop wise (significant exotherm observed). A reflux condenser was fitted to the flask with a nitrogen gas inlet and gas outlet (Tygon tubing) running into a scrubber solution of sodium sulfite (1 M, 200 mL). After the addition was complete, the reaction mixture was heated in a silicone oil bath at 80° C. for 4 h. After this time, the reaction was cooled to 10° C. and phosphorus-trichloride (4.23 ml, 48.3 mmol) was added drop-wise. The reaction was then heated to 80° C. During this time the color intensity of the reaction decreased, and after 8 h, the reaction mixture appeared dark orange. The reaction was then cooled to room temperature and diluted with ether (1 L). The ethereal solution was transferred to a separation funnel and washed with 1M sodium sulfite (2 (500 mL), water (1 (500 mL), and brine (1 (500 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to afford an oil. Ice cold pentane (50 mL) was then added to the crude product, and the mixture was stirred vigorously. After 20 min, a fine white precipitate formed, which was filtered and washed with pentane (20 mL) and then air dried under a gentle vacuum to afford (4S)-2-bromobicyclo[2.2.1]heptane-1-carboxylic acid (100.2 g, 457 mmol) as a white solid material.

1. additionAfter the addition
2. temperaturethe reaction mixture was heated in a silicone oil bath at 80° C. for 4 h
3. temperatureAfter this time, the reaction was cooled to 10° C.
4. temperatureThe reaction was then heated to 80° C
5. temperatureThe reaction was then cooled to room temperature
6. customThe ethereal solution was transferred to a separation funnel
7. washwashed with 1M sodium sulfite (2 (500 mL), water (1 (500 mL), and brine (1 (500 mL)
8. dry with materialThe organic layer was dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto afford an oil
12. stirringthe mixture was stirred vigorously
13. waitAfter 20 min
14. customa fine white precipitate formed
15. filtrationwhich was filtered
16. washwashed with pentane (20 mL)
17. customair dried under a gentle vacuum

ORD 기록

ord-40712af5ac7e4871a3772eb59450191f

출처 데이터셋

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08541592B2