1-Methyl-1H-1,2,3-triazole → (2,4-Dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Temperature

-40 °C

To a flask containing 1-methyl-1H-1,2,3-triazole (1.60 g, 19.3 mmol, Intermediate 42, step a) was added THF (200 mL) and the solution was cooled to −40° C. To this colorless homogeneous solution was added n-BuLi (2.5 M in hexanes, 7.7 mL, 19.2 mmol) dropwise which immediately afforded a dark brown viscous mixture. The mixture was kept between −10 to −20° C. for 60 min, then 2,4-dimethylthiazole-5-carbaldehyde (3.03 g, 21.5 mmol) in THF (5 mL) was introduced and the reaction mixture began to stir much more easily, but still remained brownish. Once the aldehyde was added the reaction was placed in an ice-bath and maintained there until it warmed to room temp. After 3 hours the reaction was quenched by pouring into a saturated solution of NH4Cl at room temperature. The aqueous portion was extracted with EtOAc (5×100 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give a brown oil-foam. Flash chromatography on silica gel (10-30% acetone increasing gradient to 10% MeOH-DCM) gave the title compound as a light orange foam.

1. customimmediately afforded a dark brown viscous mixture
2. customwas placed in an ice-bath
3. temperaturemaintained there until it
4. temperaturewarmed to room temp
5. customAfter 3 hours the reaction was quenched
6. additionby pouring into a saturated solution of NH4Cl at room temperature
7. extractionThe aqueous portion was extracted with EtOAc (5×100 mL)
8. washThe combined organics were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customto give a brown oil-foam

ORD record

ord-485b52320e0e41b3977d51794a3a439d

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2