Hydrochloric Acid → 2-Benzyloxy-4-benzyloxycarbonylaminomethylbenzoic acid

Temperature

75 °C

Methyl N-(benzyloxycarbonyl)-4-aminomethyl-2-O-benzylsalicylate (6.81 g, 16.8 mmoles) was dissolved in tetrahydrofaran (50 mL). A solution of lithium hydroxide monohydrate (0.78 g, 18.5 mmoles) in water (25 mL) was added, and the reaction mixture was stirred and heated at 75° C. for 24 hours. The solution was cooled, and 1N aqueous hydrochloric acid (50 mL) was added. The reaction mixture was extracted twice with ethyl acetate (150 mL then 50 mL). The combined ethyl acetate extracts were washed with water (75 mL) and saturated aqueous sodium chloride (50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to 150 mL. The ethyl acetate solution was heated to boiling, and hexanes (150 mL) was added. The solution was cooled in ice, and crystals formed. The crystals were collected by filtration, washed with hexanes, and dried in vacuo to afford 5.92 g (90% yield) of N-(benzyloxy-carbonyl)-4-aminomethyl-2-O-benzylsalicylic acid (m.p. 139°-140° C., open capillary, uncorrected).

1. temperatureThe solution was cooled
2. extractionThe reaction mixture was extracted twice with ethyl acetate (150 mL
3. washThe combined ethyl acetate extracts were washed with water (75 mL) and saturated aqueous sodium chloride (50 mL)
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated to 150 mL
7. temperatureThe ethyl acetate solution was heated
8. additionhexanes (150 mL) was added
9. temperatureThe solution was cooled in ice
10. customcrystals formed
11. filtrationThe crystals were collected by filtration
12. washwashed with hexanes
13. customdried in vacuo

ORD record

ord-5414c1e3f0e44e69a432bc2b8781f6d9

Source dataset

uspto-grants-1999_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05869623