1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [(R)-2-((R)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 246093Notes

Reaction equation

HRID 246093 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)CCCN=C=NCC.OC1C2N=NNC=2C=CC=1.Cl.[F:36][C@@H:37]1[CH2:41][CH2:40][NH:39][CH2:38]1.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH3:13])[C:10]([N:39]1[CH2:40][CH2:41][C@@H:37]([F:36])[CH2:38]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 637606BOC-D-alanineHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 178418300HCID 178418300, compound

Product 1

HCID 71280476[(R)-2-((R)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl esterYield 94.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-2-tert-Butoxycarbonylamino-propionic acid (1.0 g, 5.3 mmol), 1-(3-(dimethylamino)-propyl)-3-ethylcarbodiimide (2.33 g, 12.2 mmol) and hydroxybenzotriazole (1.64 g, 12.2 mmol) were dissolved in DMF (50 ml). (R)-3-Fluoropyrrolidine hydrochloride (1.66 g, 13.2 mmol) and N,N-diisopropylethylamine (2.95 ml, 16.9 mmol) were added and the mixture was stirred at room temperature for 16 h. Ethyl acetate was added and the solution was washed with 10% citric acid solution three times. The organic layer was washed with sodium bicarbonate solution which was then back-extracted with ethyl acetate four times. The combined organic layers were then washed further with lithium chloride solution, sodium chloride solution, and dried over magnesium sulfate. Concentration of the solution gave 1.3 g (94%) of [(R)-2-((R)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester.

Workup

  1. washthe solution was washed with 10% citric acid solution three times
  2. washThe organic layer was washed with sodium bicarbonate solution which
  3. extractionwas then back-extracted with ethyl acetate four times
  4. washThe combined organic layers were then washed further with lithium chloride solution, sodium chloride solution
  5. dry with materialdried over magnesium sulfate

Sources & evidence

ORD record
ord-03cf4a5dffa14522a3df4d493fad2b55
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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