Diisopropylamine → N,N-Dimethyl-2-(2,4-dimethoxyphenyl)-2-hydroxythioacetamide

Temperature

-78 °C

A 110 mL THF solution of lithium diisopropylamide (LDA) (80 mmol) was generated from a 1.6M hexane solution of n-butyllithium (50 mL, 80 mmol) and diisopropylamine (11.2 mL, 80 mmol) at -10° C., then cooled to -78° C. A 50 mL solution of 2,4-dimethoxybenzaldehyde (12 g, 72 mmol) and N,N-dimethylthioformamide (6.8 mL, 80 mmol) was cooled to 0° C. and added to the -78° C. LDA solution at a rate keeping the temperature less than -70° C. The reaction mixture was stirred at -75° C. for 2.5 hours, allowed to warm to 0° C., quenched with saturated aqueous NH4Cl, and extracted with EtOAc three times. The EtOAc extracts were combined, washed with brine, dried (Na2SO4), concentrated, triturated with Et2O/ pet. ether, filtered, and dried in vacuo to give 8.4 g(46% yield) of product: mp 139-140° C.; 1H NMR (CDCl3) d 3.05 (s, 3H, NCH3), 3.50 (s, 3H, NCH3), 3.80 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 5.19-5.21 (d, 1H, J=7 Hz, OH), 5.72-5.74 (d, 1H, J=7 Hz, CH), 6.43-6.47 (m, 2H, ArH), 7.24(s, 1H, ArH); MS(FD) 255 (M+). Anal. Calcd for C12H17NO3S: C, 56.45; H, 6.71; N, 5.49. Found: C, 56.64; H, 6.49; N, 5.59.

1. additionadded to the -78° C
2. customthe temperature less than -70° C
3. temperatureto warm to 0° C.
4. customquenched with saturated aqueous NH4Cl
5. extractionextracted with EtOAc three times
6. washwashed with brine
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated
9. customtriturated with Et2O/ pet. ether
10. filtrationfiltered
11. customdried in vacuo

ORD record

ord-dd4eb59466014edd94ea7e33d6fe2bc6

Source dataset

uspto-grants-1999_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05962698