Dichloromethane → HCID 66643588, compound

Temperature

-77 °C

2-(2-Phenylpropan-2-ylthio)ethanol (45.0 g, 229 mmol) was weighed into a 1 L 3-neck round-bottomed flask which was then attached to a 125 mL pressure-equalising funnel (centre-socket), a Suba-seal (side-arm) and a double layer coil condenser (side-arm) which was connected in turn to a nitrogen-vacuum manifold. The apparatus was then purge-filled with nitrogen three times. Dichloromethane (anhydrous, 300 mL) was then cannula transferred into the reaction flask. DIPEA (anhydrous, 60 mL) was then added to the reaction solution using a 20 mL gastight syringe (3×20 mL transfers). Freshly distilled acryloyl chloride (22.35 mL) was then placed in the pressure-equalising addition funnel. The reaction flask was then surrounded with a dry-ice/acetone cooling bath and the reaction mixture cooled to a temperature of −77° C. The acryloyl chloride was then added slowly dropwise to the chilled reaction mixture under nitrogen over a period of 90 minutes (ca. 1 drop every 2 seconds). The reaction mixture was then stirred in the cooling bath under nitrogen overnight and allowed to warm slowly to room temperature. Next day the reaction flask was surrounded with a water/ice cooling bath and methanol (50 mL) was added to the pressure-equalising addition funnel. The reaction mixture was cooled to <5° C. and the methanol then added dropwise over a period of 30 minutes in order to quench the excess acryloyl chloride. The reaction mixture was then allowed to warm to room temperature before being extracted with 1×300 mL portion of 1M HCl (aq) and 2×300 mL portions of brine. The organic layer was then partitioned and separated and then dried over anhydrous magnesium sulfate for a period of 1 hour. The drying mixture was then filtered and the collected solid washed with 3×40 mL portions of dichloromethane. The filtrate and washings were combined and then CAREFULLY stripped to dryness in vacuo (rotary evaporator) at a bath temperature of 25° C. The resultant orange liquid (with a small quantity of white “gel-like” material on the walls of the evaporation flask, presumably polymer) was distilled in vacuo through a Claisen head with a spatula measure of 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethyl-1,1′-spirobisindane inhibitor added to the distillation mixture.

1. customwhich was then attached to a 125 mL pressure-equalising funnel
2. custom(centre-socket), a Suba-seal (side-arm) and a double layer coil condenser (side-arm) which
3. additionThe apparatus was then purge-filled with nitrogen three times
4. customThe reaction flask was then surrounded with a dry-ice/acetone cooling bath
5. temperatureto warm slowly to room temperature
6. customNext day the reaction flask was surrounded with a water/ice cooling bath
7. temperatureThe reaction mixture was cooled to <5° C.
8. customto quench the excess acryloyl chloride
9. temperatureto warm to room temperature
10. extractionbefore being extracted with 1×300 mL portion of 1M HCl (aq) and 2×300 mL portions of brine
11. customThe organic layer was then partitioned
12. customseparated
13. dry with materialdried over anhydrous magnesium sulfate for a period of 1 hour
14. filtrationThe drying mixture was then filtered
15. washthe collected solid washed with 3×40 mL portions of dichloromethane
16. customCAREFULLY stripped to dryness in vacuo (rotary evaporator) at a bath temperature of 25° C
17. distillationThe resultant orange liquid (with a small quantity of white “gel-like” material on the walls of the evaporation flask, presumably polymer) was distilled in vacuo through a Claisen head with a spatula measure of 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethyl-1,1′-spirobisindane
18. additioninhibitor added to the distillation mixture

ORD record

ord-31ec33ce6ba54505b86c390395e26d89

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729203B2