Toluene → HCID 67715899, compound

Temperature

1 °C

A 3-liter 3-necked flask is equipped with an overhead stirrer, a nitrogen inlet and an addition funnel. The flask is charged with tetrahydrofuran (256 mL; KF<70 mcg/mL) and the toluene solution of the sulfonamide 13b (125 mL containing 48.5 g, 0.228 mol, 1.8M solution in toluene-0.389 g/mL). The mixture is cooled to 1° C. The KF of the solution is 70 mcg/mL. The n-butyllithium (1.6M in hexanes, 302 mL, 0.48 mol) is charged into the addition funnel and added dropwise over 55 min., maintaining a temperature <5° C. The mixture is aged for 2 hours and triisopropylborate (63 mL, 0.273 mol, d=0.815) is added to the suspension over 70 min. The temperature is maintained <2° C. After 1 hour, the reaction is 94% complete by HPLC. The reaction must be quenched once the assay indicates completion since the product will slowly decompose in the reaction mixture. HPLC conditions: column: Zorbax RX-C8; gradient elution with CH3CN/water/H3PO4 from 30:70:0.1 to 60:40:0.1 over 15 min.; flow rate=1.0 mL/min.; UV detection at 228 nm.; Retention time: t-Butyl sulfonamidophenylboronic acid 13, 8.5 min. The reaction is quenched by the addition of water (50 mL) at 0° C. The temperature is maintained <10° C. Concentrated hydrochloric acid (42 mL) is added dropwise, maintaining the temperature <10° C. The layers are separated and the organic phase is washed with water (50 mL), then brine (50 mL). The organic phase is concentrated to 100 mL trader vacuum at an internal temperature <30° C. The solution is diluted to 350 mL with n-butanol and concentrated to 225 mL under vacuum providing a 1M solution of the sulfonamido phenylboronic acid 13 (54 g) for a 90% yield. The vacuum concentration at an internal temperature <30° C. is required to minimize deboronation. A concentration range of 0.8-1.2M in butanoI has performed successfully in the subsequent coupling reaction.

1. customA 3-liter 3-necked flask is equipped with an overhead stirrer, a nitrogen inlet and an addition funnel
2. additionadded dropwise over 55 min.
3. temperaturemaintaining a temperature <5° C
4. temperatureThe temperature is maintained <2° C
5. waitAfter 1 hour
6. customThe reaction
7. custommust be quenched once the assay
8. washgradient elution with CH3CN/water/H3PO4 from 30:70:0.1 to 60:40:0.1 over 15 min.
9. customt-Butyl sulfonamidophenylboronic acid 13, 8.5 min
10. customThe reaction is quenched by the addition of water (50 mL) at 0° C
11. temperatureThe temperature is maintained <10° C
12. additionConcentrated hydrochloric acid (42 mL) is added dropwise
13. temperaturemaintaining the temperature <10° C
14. customThe layers are separated
15. washthe organic phase is washed with water (50 mL)
16. concentrationThe organic phase is concentrated to 100 mL trader vacuum at an internal temperature <30° C
17. additionThe solution is diluted to 350 mL with n-butanol
18. concentrationconcentrated to 225 mL under vacuum

ORD record

ord-4f6580c685a746509ba4a40c2fcb116a

Source dataset

uspto-grants-1997_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05693812