Trimethylsilyl iodide → (S)-3-Amino-N-cyclopropyl-N-(2,3-dichlorobenzyl)-4-hydroxybutanamide

HRID 1092799Notes

Reaction equation

HRID 1092799 reaction equation
C(OC(=O)[NH:10][C@@H:11]([CH2:14][C:15]([N:17]([CH:27]1[CH2:29][CH2:28]1)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=1[Cl:26])=[O:16])[CH2:12][OH:13])C1C=CC=CC=1.C[Si](I)(C)C>C(#N)C>[NH2:10][C@H:11]([CH2:12][OH:13])[CH2:14][C:15]([N:17]([CH:27]1[CH2:29][CH2:28]1)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=1[Cl:26])=[O:16]

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 66593948(S)-Benzyl-4-(cyclopropyl(2,3-dichlorobenzyl)amino)-1-hydroxy-4-oxobutan-2-ylcarbamate

Product 1

HCID 66590104(S)-3-Amino-N-cyclopropyl-N-(2,3-dichlorobenzyl)-4-hydroxybutanamideYield 82.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Into a 1L round bottom flask fitted with a nitrogen inlet was added 4A (18.3 g, 40.6 mmol) and acetonitrile (450 mL). Trimethylsilyliodide (TMSI) (17.4 mL, 121.7 mmol, 3 eq) was added quickly at room temperature. After stirring for 15 minutes, the reaction was quenched with 50 mL of methanol. The solvent was removed under vacuum. The residue was partitioned between ethyl acetate (100 mL) and saturated sodium bicarbonate (50 mL). The organic layer was separated and the aqueous layer was extracted further with ethyl acetate (2×50 mL). The organic layers were combined and washed once with brine (50 mL). The organic phase was dried over sodium sulfate and filtered. Solvent was removed under vacuum and the residue was purified by column chromatography (5% methanol/1% triethylamine/DCM) to give 10.6 g of 4B (69%). ESI-MS:m/z 317.3 (M+H)+.

Workup

  1. customthe reaction was quenched with 50 mL of methanol
  2. customThe solvent was removed under vacuum
  3. customThe residue was partitioned between ethyl acetate (100 mL) and saturated sodium bicarbonate (50 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted further with ethyl acetate (2×50 mL)
  6. washwashed once with brine (50 mL)
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. customSolvent was removed under vacuum
  10. customthe residue was purified by column chromatography (5% methanol/1% triethylamine/DCM)

Sources & evidence

ORD record
ord-7f013cf4e19d4899898a24a652f15136
Source dataset
uspto-grants-2012_03
Patent number
US08129538B1

Reaction notes

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