Citric Acid → HCID 86618515, compound

HRID 1010568Notes

Reaction equation

HRID 1010568 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@@H:13]([CH3:14])[CH2:12][NH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:15][C:16]1[C:17]([F:29])=[C:18]([CH:24]=[C:25]([F:28])[C:26]=1F)[C:19]([O:21][CH2:22][CH3:23])=[O:20].N12CCCN=C1CCCCC2.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@@H:13]([CH3:14])[CH2:12][N:11]([C:26]2[C:25]([F:28])=[CH:24][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:17]([F:29])[C:16]=2[CH3:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 11138119(3S,4S)-3-(Boc-amino)-4-methylpyrrolidineHCID 21220461Ethyl 2,4,5-trifluoro-3-methylbenzoate

Product 1

HCID 86618515HCID 86618515, compoundYield 70.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidine (1.80 g, 8.97 mmol), ethyl 3-methyl-2,4,5-trifluorobenzoate (2.18 g, 10.0 mmol), and 1,8-diazabicyclo[5.4.0]undeca-7-ene (DBU) (2.24 mL, 15 mmol) in dimethyl sulfoxide (20 mL) was stirred under a nitrogen atmosphere at an external temperature of 60° C. for 70 hours. The temperature of the mixture was cooled to room temperature. The resultant mixture was poured to a 10% aqueous citric acid solution, followed by extraction with ethyl acetate (200 mL×3), washing by water (200 mL), saturated aqueous sodium hydrogencarbonate (150 mL), and saturated brine (150 mL), and dried over anhydrous sodium magnesium. After filtration, the filtrate was concentrated under reduced pressure. The obtained residue was purified through silica gel column chromatography (n-hexane:ethyl acetate=6:1), to thereby yield the title compound as colorless crystals (2.51 g, 70.2%).

Workup

  1. extractionfollowed by extraction with ethyl acetate (200 mL×3)
  2. washwashing by water (200 mL), saturated aqueous sodium hydrogencarbonate (150 mL), and saturated brine (150 mL)
  3. dry with materialdried over anhydrous sodium magnesium
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified through silica gel column chromatography (n-hexane:ethyl acetate=6:1)

Sources & evidence

ORD record
ord-86c0637d4c04490caebdbf39cd6d30ae
Source dataset
uspto-grants-2011_07
Patent number
US07977327B2

Reaction notes

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