Reacción #74389

Ecuación de reacción

phosphorus-trichloride

Tygon

sodium sulfite

(1S,4R)-bicyclo[2.2.1]heptane-2-carboxylic acid

bromine

→

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

Disolventes

ether

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONAfter the addition
2. 2
   Temperaturathe reaction mixture was heated in a silicone oil bath at 80° C. for 4 h
3. 3
   TemperaturaAfter this time, the reaction was cooled to 10° C.
4. 4
   TemperaturaThe reaction was then heated to 80° C
5. 5
   TemperaturaThe reaction was then cooled to room temperature
6. 6
   OtroThe ethereal solution was transferred to a separation funnel
7. 7
   Lavadowashed with 1M sodium sulfite (2 (500 mL), water (1 (500 mL), and brine (1 (500 mL)
8. 8
   SecadoThe organic layer was dried over MgSO4
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated in vacuo
11. 11
    Otroto afford an oil
12. 12
    workup.STIRRINGthe mixture was stirred vigorously
13. 13
    workup.WAITAfter 20 min
14. 14
    Otroa fine white precipitate formed
15. 15
    Filtraciónwhich was filtered
16. 16
    Lavadowashed with pentane (20 mL)
17. 17
    Otroair dried under a gentle vacuum

Procedimiento

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.

Fuente