Triethylamine → HCID 60054136, compound

HRID 488361Notes

Reaction equation

HRID 488361 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH2:15][C@H:14]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])[O:13][C:12]3=[O:21])=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.C(N(CC)CC)C.[C:29]([O:32][CH2:33][C:34](Cl)=[O:35])(=[O:31])[CH3:30]>C(Cl)Cl>[C:29]([O:32][CH2:33][C:34]([N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[C:7]([N:11]3[CH2:15][C@H:14]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])[O:13][C:12]3=[O:21])[CH:6]=2)[CH2:1]1)=[O:35])(=[O:31])[CH3:30]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 26297Acetoxyacetyl chlorideHCID 69734604HCID 69734604, compound

Product 1

HCID 60054136HCID 60054136, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-[[(5S)-3-[1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (Example 1, Step 6, 350 mg, 1.21 mmol) and triethylamine (0.252 mL, 1.81 mmol) in dry CH2Cl2 (6 mL) under N2 is cooled to 0° C. and treated with acetoxyacetyl chloride (0.156 mL, 1.45 mmol). The resulting mixture is stirred at 0° C. for 1 hr and is then warmed to ambient temperature, diluted with CH2Cl2 (20 mL), washed with H2O (10 mL) and brine (10 mL), dried over Na2SO4 and concentrated under reduced pressure. The crude product is chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge, eluting with a gradient of MeOH/CH2Cl2 (1/99-3/97), and those fractions with an Rf=0.44 by TLC (MeOH/CHCl3, 10/90) are pooled and concentrated to give 323 mg (69%) of the title compound as a glassy solid. An analytical sample is prepared by trituration and filtration from Et2O. MS (ESI+) for C19H23N3O6 m/z 390 (M+H)+; Anal. Calcd for C19H23N3O6: C, 58.60; H, 5.95; N, 10.79. Found: C, 58.46; H, 6.06; N, 10.66; [α]25D =−18° (c 0.93, DMSO).

Workup

  1. temperatureis then warmed to ambient temperature
  2. washwashed with H2O (10 mL) and brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product is chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge
  6. washeluting with a gradient of MeOH/CH2Cl2 (1/99-3/97)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-da6b85365b2046fd839578eff8c7ddf2
Source dataset
uspto-grants-2005_12
Patent number
US06972286B2

Reaction notes

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