Chloroacetaldehyde → HCID 66970903, compound

HRID 1361312Notes

Reaction equation

HRID 1361312 reaction equation
Cl.C(N1C[C@@H](C2C=CC(F)=CC=2F)[C@H](C([N:21]2[C@@H:25]([C:26]3[S:27][CH:28]=[CH:29][N:30]=3)[CH2:24][C@H:23]([N:31]([CH:38]3[CH2:43][CH2:42][C:41]([CH3:45])([CH3:44])[CH2:40][CH2:39]3)[C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:22]2)=O)C1)(C)(C)C.Cl[CH2:47]C=O.[C:50]([O-:53])(O)=[O:51].[Na+].N1[CH:60]=[CH:59][CH:58]=CC=1.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C(COC)OC>[C:50]([N:21]1[CH2:22][C@@H:23]([N:31]([CH:38]2[CH2:39][CH2:40][C:41]([CH3:45])([CH3:44])[CH2:42][CH2:43]2)[C:32](=[O:37])[C:33]([CH3:36])([CH3:34])[CH3:35])[CH2:24][C@@H:25]1[C:26]1[S:27][CH:28]=[CH:29][N:30]=1)([O:53][C:59]([CH3:58])([CH3:60])[CH3:47])=[O:51]

Participants

7

Reactant 5

HCID 33ChloroacetaldehydeHCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 516892Sodium BicarbonateHCID 66970943HCID 66970943, compound

Product 1

HCID 66970903HCID 66970903, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of BOC (2R,4S)-2-(aminocarbonothionyl)-4-[(4,4-dimethylcyclohexyl)(2,2-dimethylpropanoyl)amino pyrrolidine (880 mg, 2 mmol) prepared in Step A in dimethoxyethane (10 ml) was added 50 wt % chloroacetaldehyde (0.38 ml, 3 mmol) and NaHCO3 (504 mg, 6 mmol), and stiffed at rt for 2 h. After the reaction finished, the reaction solution was concentrated in vacuo, and extracted with EtOAC. The organic extracts were washed with water and brine, dried over MgSO4, concentrated in vacuo, and the residue was purified by column chromatography (eluent: EtOAc:Hex=1/1). This compound (510 mg, 1.24 mmol) was dissolved in pyridine (0.9 ml, 11.1 mmol), and TFAA (1.0 g, 4.96 mmol) was added dropwise at 0° C. At the same temperature, the solution was stirred for 1.5 h, concentrated in vacuo, and extracted with EtOAc. The organic extracts were washed with 0.5N HCl solution and brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by column chromatography (eluent: EtOAc/Hex=2/1) to give the title compound (249 mg, 51.0%).

Workup

  1. concentrationthe reaction solution was concentrated in vacuo
  2. extractionextracted with EtOAC
  3. washThe organic extracts were washed with water and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customthe residue was purified by column chromatography (eluent: EtOAc:Hex=1/1)
  7. concentrationconcentrated in vacuo
  8. extractionextracted with EtOAc
  9. washThe organic extracts were washed with 0.5N HCl solution and brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by column chromatography (eluent: EtOAc/Hex=2/1)

Sources & evidence

ORD record
ord-3e037d88c71145c4b5087b73e1cb55a1
Source dataset
uspto-grants-2011_02
Patent number
US07879852B2

Reaction notes

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