Borane → 2-O-tert-butyl 4-O-ethyl 5-(3-hydroxypropyl)-3-methyl-1H-pyrrole-2,4-dicarboxylate

5-(2-Carboxy-ethyl)-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 1e (9.75 g, 30 mmol) was dissolved in 90 ml of anhydrous tetrahydrofuran under stirring, and added dropwise slowly with a solution of borane in tetrahydrofuran (90 ml, 1 mol/L, 90 mmol) to the solution while maintaining the temperature at −10˜−5° C. in an ice-salt bath under an argon atmosphere. Upon completion of the addition, the ice-salt bath was removed and the reaction mixture was allowed to warm up to room temperature and stirred for 2-3 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was concentrated under reduced pressure to evaporate the solvent. The residue was added with 100 ml of saturated sodium bicarbonate solution and 100 ml of ethyl acetate, and stirred until dissolved. The resulting mixture was extracted with ethyl acetate (100 ml×3). The combined organic extracts were washed with 100 ml of saturated brine, dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to obtain the title compound 5-(3-hydroxy-propyl)-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 1f (9.2 g, yield 98%) as a light yellow oil.

1. temperaturewhile maintaining the temperature at −10˜−5° C. in an ice-salt bath under an argon atmosphere
2. additionUpon completion of the addition
3. customthe ice-salt bath was removed
4. stirringstirred for 2-3 hours
5. concentrationthe reaction mixture was concentrated under reduced pressure
6. customto evaporate the solvent
7. additionThe residue was added with 100 ml of saturated sodium bicarbonate solution and 100 ml of ethyl acetate
8. stirringstirred
9. dissolutionuntil dissolved
10. extractionThe resulting mixture was extracted with ethyl acetate (100 ml×3)
11. washThe combined organic extracts were washed with 100 ml of saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationfiltered
14. customto remove the drying agent
15. concentrationconcentrated under reduced pressure

ORD record

ord-03b26a64ef5d4cb29395728fa1055af1

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329682B2