Methyl chloroformate → HCID 60054152, compound

HRID 488359Notes

Reaction equation

HRID 488359 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([O-])(O)=O.[Na+].Cl[C:28]([O:30][CH3:31])=[O:29]>C1COCC1.O.CCOC(C)=O>[C:18]([NH:17][CH2:16][C@@H:14]1[O:13][C:12](=[O:21])[N:11]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[CH2:1][N:2]([C:28]([O:30][CH3:31])=[O:29])[CH2:3][CH2:4]3)[CH2:15]1)(=[O:20])[CH3:19]

Participants

7

Reactant 3

HCID 6586Methyl chloroformateHCID 516892Sodium BicarbonateHCID 69734604HCID 69734604, compound

Product 1

HCID 60054152HCID 60054152, compoundYield 88.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-[[(5S)-3-[1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (Step 6, 450 mg, 1.55 mmol) and NaHCO3 (260 mg, 3.10 mmol) in THF (15.5 mL) under N2 is treated with methyl chloroformate (0.144 mL, 1.87 mmol) with vigorous stirring. A thick, white slurry results which is redissolved by the addition of H2O (approx. 2 mL). The mixture is stirred at ambient temperature for 1 hr and is then diluted with H2O (10 mL) and EtOAc (20 mL) and the layers are separated. The aqueous phase is reextracted with CH2Cl2 (20 mL), and the combined organic phase is washed with brine (10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product is chromatographed on silica gel (45 g, 230-400 mesh), eluting with MeOH/CHCl3 (2/98), and those fractions with an Rf=0.51 by TLC (MeOH/CHCl3, 10/90) are pooled and concentrated to give 475 mg (88%) of the title compound as a glassy solid. 1H NMR (400 MHz, CDCl3) δ 7.32 (m, 2H), 7.11 (m, 1H), 6.19 (m, 1H), 4.76 (m, 1H), 4.59 (s, 2H), 4.05 (t, 1H), 3.78 (dd, 1H), 3.75 (s, 3H), 3.75-3.50 (m, 4H), 2.85 (m, 2M), 2.02 (s, 3H); MS (ESI+) for C17H21N3O5 m/z 348 (M+H)+; [α]25D=−20° (c 1.04, DMSO).

Workup

  1. customA thick, white slurry results which
  2. customthe layers are separated
  3. washthe combined organic phase is washed with brine (10 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product is chromatographed on silica gel (45 g, 230-400 mesh)
  7. washeluting with MeOH/CHCl3 (2/98)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-97250abf90e94309b3edb70838718a4d
Source dataset
uspto-grants-2005_12
Patent number
US06972286B2

Reaction notes

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