Formamide → HCID 57907619, compound

HRID 243720Notes

Reaction equation

HRID 243720 reaction equation
[NH2:1][N:2]1[C@H:6]([CH2:7][O:8][C:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:5][CH2:4][C:3]1=O.[CH:29]([NH2:31])=O>CN(C=O)C.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[C:9]([O:8][CH2:7][C@H:6]1[N:2]2[N:1]=[CH:29][N:31]=[C:3]2[CH2:4][CH2:5]1)([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 2

HCID 713FormamideHCID 57907607HCID 57907607, compound

Product 1

HCID 57907619HCID 57907619, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

To a stirred solution of 0.540 g (1.45 mmol) of (5S)-1-amino-5-[(trityloxy)methyl]pyrrolidin-2-one from step A above in 5 mL of anhydrous DMF was added 0.327 g (7.25 mmol) of formamide followed by 0.050 g (0.36 mmol) of zinc(II) chloride. The resulting mixture was heated to 160° C. for 48 h, cooled to ambient temperature and diluted with 25 mL of ethyl acetate. The solution was washed sequentially with an aqueous sodium bicarbonate solution, water and then brine and the organic layer dried over magnesium sulfate. The mixture was then filtered, evaporated to dryness in vacuo and purified by silica gel chromatography eluting with a 0-100% ethyl acetate in hexanes gradient to afford the title compound (0.27 g, 49%). LC-MS: m/z (ES) 382 (MH)+.

Workup

  1. temperaturecooled to ambient temperature
  2. washThe solution was washed sequentially with an aqueous sodium bicarbonate solution, water
  3. dry with materialbrine and the organic layer dried over magnesium sulfate
  4. filtrationThe mixture was then filtered
  5. customevaporated to dryness in vacuo
  6. custompurified by silica gel chromatography
  7. washeluting with a 0-100% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-2a0483ffe1674772af2ad0fb5d3d2296
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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