Chloroacetaldehyde → HCID 118511939, compound

HRID 1056126Notes

Reaction equation

HRID 1056126 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C@@H:11]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])/[C:12](/O)=[CH:13]/[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH3:30].[C:31]([O-])(=O)[CH3:32].[NH4+].ClCC=O>>[C:17]([O:16][C:14]([C:13]1[CH:32]=[CH:31][NH:30][C:12]=1[C@H:11]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:10][CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 4

HCID 33ChloroacetaldehydeHCID 222AmmoniaHCID 517165Ammonium AcetateHCID 89782120HCID 89782120, compound

Product 1

HCID 118511939HCID 118511939, compoundYield 61.8%

Conditions

Temperature
50 °C

Procedure

(R)-tert-Butyl 6-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-3-oxohexanoate (724a, 6.60 g, 16.20 mmol) was treated with NH3 (2 M in MeOH, 81 mL, 162 mmol) and ammonium acetate (9.36 g, 121 mmol) at RT. The resulting mixture was stirred for at 50° C. for 30 min, then treated with chloroacetaldehyde (50 wt % in water, 10.42 mL, 81 mmol) and stirred at 50° C. for 2 h. The reaction mixture was stirred at RT overnight (16 h). The reaction mixture was concentrated to remove most of MeOH and partitioned between sat'd NaHCO3 (100 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (2×50 mL), and the combined organic extracts were washed with water and brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure (rotary evaporator) to afford the crude product as a brown oil. The crude residue was purified on an ISCO Combiflash RF (160 g Thomson SingleStep column, using a gradient of 0-10% EtOAc in DCM) affording (R)-tert-butyl 2-(3-(benzyloxy)-1-((tert-butoxycarbonyl)amino)propyl)-1H-pyrrole-3-carboxylate (724b, 4.31 g, 10.01 mmol, 61.8% yield) as a light yellow viscous oil upon concentration of the product containing fractions. m/z (ESI, +ve) 453.2 (M+Na)+.

Workup

  1. stirringstirred at 50° C. for 2 h
  2. stirringThe reaction mixture was stirred at RT overnight (16 h)
  3. concentrationThe reaction mixture was concentrated
  4. customto remove most of MeOH
  5. custompartitioned between sat'd NaHCO3 (100 mL) and EtOAc (100 mL)
  6. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  7. washthe combined organic extracts were washed with water and brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure (rotary evaporator)
  11. customto afford the crude product as a brown oil
  12. customThe crude residue was purified on an ISCO Combiflash RF (160 g Thomson SingleStep column

Sources & evidence

ORD record
ord-9ae2372eeb8d4838a8cb7c1885c53480
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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