Dimethylformamide → Ethyl (2R)-2-(6-chloro-1H-benzimidazole-2-yl)-2-hydroxy-3-phenylpropanoate

HRID 717312Notes

Reaction equation

HRID 717312 reaction equation
[CH2:1]([C@:8]([OH:17])([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:9](O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:42][C:43]1[CH:44]=[C:45]([Cl:50])[CH:46]=[CH:47][C:48]=1[NH2:49].CN(C=O)C>C(OCC)(=O)C.O>[Cl:50][C:45]1[CH:46]=[CH:47][C:48]2[N:49]=[C:9]([C@:8]([OH:17])([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH:42][C:43]=2[CH:44]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 72634-Chloro-1,2-diaminobenzeneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71727620(2R)-2-benzyl-3-ethoxy-2-hydroxy-3-oxopropanoic acid

Product 1

HCID 90395277Ethyl (2R)-2-(6-chloro-1H-benzimidazole-2-yl)-2-hydroxy-3-phenylpropanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (2R)-2-benzyl-3-ethoxy-2-hydroxy-3-oxopropanoic acid (320 mg), HATU (562 mg), 3,4-diamino-chlorobenzene (230 gm) was added 4 mL of DMF at rt. The mixture was stirred at rt overnight. To this mixture was added water and ethyl acetate. The organic layer was washed with water and then concentrated in vacuo after being dried with mangesium sulfate. The residue, without purification, was dissolved in 3 mL of acetic acid and heated at 75 degrees for 2 h. The mixture was then concentrated and purified by Biotage silica gel column chromatography (8-35% ethyl acetate in hexanes) to give the title product.

Workup

  1. washThe organic layer was washed with water
  2. concentrationconcentrated in vacuo
  3. dry with materialafter being dried with mangesium sulfate
  4. customThe residue, without purification
  5. dissolutionwas dissolved in 3 mL of acetic acid
  6. temperatureheated at 75 degrees for 2 h
  7. concentrationThe mixture was then concentrated
  8. custompurified by Biotage silica gel column chromatography (8-35% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-18194b9a56fd4636a005a5fff3cd142c
Source dataset
uspto-grants-2015_11
Patent number
US09193717B2

Reaction notes

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