Ethyl 4-phenyl-1,3-thiazole-2-carboxylate → (4-Phenyl-1,3-thiazol-2-yl)methanol

Temperature

-40 °C

A solution of ethyl 4-phenylthiazole-2-carboxylate (Example 4B, 1.300 g, 5.57 mmol) in diethyl ether (60 mL) in a 500 mL flask under a nitrogen atmosphere was cooled to −40° C. (dry ice-water-calcium chloride bath) and treated with solid LiAH4 (0.40 g, 10.54 mmol) added all at once. The mixture was stirred at −40° C. over 2.5 h. The reaction was quenched by dropwise addition of ethyl acetate (1 mL), water (0.4 mL) followed by 15% aqueous sodium hydroxide (0.4 mL) and water (1.2 mL). The bath was then removed and the mixture was stirred at room temperature for 50 min. The solid formed was filtered and washed with ether (50 mL). The combined filtrate and washing was washed with brine (20 mL) and dried over anhydrous magnesium sulfate. Evaporation gave a yellow oil which was purified by silica gel chromatography (2.5×8 cm, elution toluene-ethyl acetate 9:1, 8:2 to 7:3). The resulting light yellow oil (0.931 g) was then distilled in vacuo (bp: 105-110° C./0.1 torr, bulb to bulb, air bath temperature) to provide the title material (0.918 g, 86%) of a colorless syrup. LC (Method C): 1.672 min. HRMS (ESI) calcd for C10H10NOS [M+H]+ m/z 192.0478, found 192.0508. 1H NMR (CDCl3, 400 MHz) δ ppm: 2.90 (br t, 1H), 5.02 (d, J=4.30 Hz, 2H), 7.31-7.38 (m, 1H), 7.39-7.45 (m, 2H), 7.46 (d, J=0.8 Hz, 1H), 7.85-7.92 (m, 2H).

1. additiontreated with solid LiAH4 (0.40 g, 10.54 mmol)
2. additionadded all at once
3. customThe reaction was quenched by dropwise addition of ethyl acetate (1 mL), water (0.4 mL)
4. customThe bath was then removed
5. stirringthe mixture was stirred at room temperature for 50 min
6. customThe solid formed
7. filtrationwas filtered
8. washwashed with ether (50 mL)
9. washThe combined filtrate and washing
10. washwas washed with brine (20 mL)
11. dry with materialdried over anhydrous magnesium sulfate
12. customEvaporation
13. customgave a yellow oil which
14. customwas purified by silica gel chromatography (2.5×8 cm, elution toluene-ethyl acetate 9:1, 8:2 to 7:3)
15. distillationThe resulting light yellow oil (0.931 g) was then distilled in vacuo (bp: 105-110° C./0.1 torr, bulb to bulb, air bath temperature)

ORD record

ord-73aba03678334d3c85edca474f78a371

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303065B2