Trimethyl borate → 3-Methyl-4-nitrobenzyl alcohol

Temperature

65 °C

A flask purged with nitrogen was charged with 3-methyl-4-nitro-benzoic acid (72.5 g, 0.400 mol), trimethyl borate (166.2 g, 1.600 mol) and dry tetrahydrofuran (1449 mL). A solution of borane dimethyl sulfide complex (63.8 g, 79.8 mL, 0.840 mol) was added drop-wise to the stirred batch at 20-35° C. over at least 30 min. An exotherm and effervescence were observed during the addition. The mixture was stirred at 65° C. for at least 6 h or until in-process HPLC analysis showed that conversion was greater than 97%. Reaction was quenched at 20-40° C. with cooling by drop-wise addition of methanol (46 mL) followed by aq 5 N hydrochloric acid (144 mL) over at least 30 min. Exotherm and effervescence were observed during the quench. After stirring the batch at 50° C. for at least 1 h, it was concentrated under reduced pressure to a volume of 360 mL. The concentrated batch was washed with water (453 mL) and the solids were collected on a filter. The wet filter cake was dissolved in CH2Cl2 (2170 mL) at and the resulting solution dried over anhydrous magnesium sulfate (36 g). The dried filtrate solution containing the title compound (˜67 g, 100% yield) was used directly in the preparation of 3-methyl-4-nitro-benzaldehyde.

1. customA flask purged with nitrogen
2. additionA solution of borane dimethyl sulfide complex (63.8 g, 79.8 mL, 0.840 mol) was added drop-wise to the stirred batch at 20-35° C. over at least 30 min
3. additionAn exotherm and effervescence were observed during the addition
4. customReaction
5. customwas quenched at 20-40° C.
6. temperaturewith cooling by drop-wise addition of methanol (46 mL)
7. waitfollowed by aq 5 N hydrochloric acid (144 mL) over at least 30 min
8. stirringAfter stirring the batch at 50° C. for at least 1 h
9. concentrationit was concentrated under reduced pressure to a volume of 360 mL
10. washThe concentrated batch was washed with water (453 mL)
11. customthe solids were collected on a filter
12. dissolutionThe wet filter cake was dissolved in CH2Cl2 (2170 mL) at and the resulting solution
13. dry with materialdried over anhydrous magnesium sulfate (36 g)

ORD record

ord-74ad82bff00046efbdff686e70db9806

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365575B2