Chlorotrimethylsilane → HCID 86650528, compound

HRID 403448Notes

Reaction equation

HRID 403448 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:20])[CH2:15][CH2:16][CH2:17][C:18]#[CH:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[Mg+2].[Cl-].[CH2:24](N(CC)CC)C.[Cl:31][C:32]1[N:37]=[CH:36][C:35]([CH:38]=[O:39])=[CH:34][CH:33]=1.Cl[Si](C)(C)C>C(OCC)(=O)C>[CH2:1]([C@H:8]1[CH2:24][CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:20])[C@@H:15]([C@@H:38]([C:35]1[CH:36]=[N:37][C:32]([Cl:31])=[CH:33][CH:34]=1)[OH:39])[CH2:16][CH2:17][C:18]#[CH:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 27640536-Chloropyridine-3-carbaldehydeHCID 5360315Magnesium ChlorideHCID 57907447HCID 57907447, compound

Product 1

HCID 86650528HCID 86650528, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 23.0 g (837 mmol) of (4S)-4-benzyl-3-hex-5-ynoyl-1,3-oxazolidin-2-one from step A above in 200 mL of anhydrous ethyl acetate at ambient temperature under an atmosphere of nitrogen was added 1.6 g (17 mmol) of anhydrous magnesium chloride, 23.0 mL (166 mmol) of triethylamine, 14.0 g (100 mmol) of 6-chloropyridine-3-carboxaldehyde and 16.0 mL (124 mmol) of chlorotrimethylsilane and the resulting mixture was stirred for 72 h. The heterogeneous reaction mixture was filtered through a 300 mL plug of silica gel eluting with an additional 1 L of ethyl acetate. The filtrate was evaporated to dryness in vacuo and the residue suspended in 200 mL of methanol and 5.0 mL of trifluoroacetic acid. The resulting mixture was stirred at ambient temperature under nitrogen for 5 hours during which time the reaction became homogeneous. All volatiles were then removed in vacuo and the residue was purified by silica gel chromatography eluting with a 10-15% ethyl acetate in hexanes gradient to afford the title compound as a white solid (30 g, 88%). LC-MS: m/z (ES) 413.2 (MH)+.

Workup

  1. filtrationThe heterogeneous reaction mixture was filtered through a 300 mL plug of silica gel eluting with an additional 1 L of ethyl acetate
  2. customThe filtrate was evaporated to dryness in vacuo
  3. stirringThe resulting mixture was stirred at ambient temperature under nitrogen for 5 hours during which time the reaction
  4. customAll volatiles were then removed in vacuo
  5. customthe residue was purified by silica gel chromatography
  6. washeluting with a 10-15% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-fd349ef910ad4841bba622125d518a63
Source dataset
uspto-grants-2014_06
Patent number
US08748433B2

Reaction notes

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