Pyridine → HCID 69734019, compound

HRID 488357Notes

Reaction equation

HRID 488357 reaction equation
[NH2:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH2:15][N:14]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:13][CH2:12]3)[CH2:4]1.N1C=CC=CC=1.[C:35](OC(=O)C)(=[O:37])[CH3:36]>C(Cl)Cl>[C:35]([NH:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH2:15][N:14]([C:19]([O:21][CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[O:20])[CH2:13][CH2:12]3)[CH2:4]1)(=[O:37])[CH3:36]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 69733820HCID 69733820, compound

Product 1

HCID 69734019HCID 69734019, compoundYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of phenylmethyl 6-[(5S)-5-(aminomethyl)-2-oxo-3-oxazolidinyl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Step 4, 1.75 g, 4.59 mmol) and pyridine (1.11 mL, 13.77 mmol) in dry CH2Cl2 (23 mL) under N2 is treated with acetic anhydride (0.649 mL, 6.88 mmol), and the mixture is stirred at ambient temperature for 3.5 hrs. The mixture is then washed with H2O (2×15 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 (0.5/99.5-2/98), and those fractions with an Rf=0.25 by TLC (MeOH/CHCl3, 5/95) are pooled and concentrated to give 1.81 g (93%) of the title compound as an amorphous, white solid. 1H NMR (400 MHz, CDCl3) δ 7.35 (m, 7H), 7.11 (m, 1H), 6.11 (m, 1H), 5.19 (s, 2H), 4.78 (m, 1H), 4.62 (s, 2H), 4.05 (t, 1H), 3.78 (dd, 1H), 3.70 (m, 3H), 3.60 (m, 1H), 2.86 (m, 2H), 2.02 (s, 3H); MS (ESI+) for C23H25N3O5 m/z 424 (M+H)+; [α]25D=−17° (c 0 77, DMSO).

Workup

  1. washThe mixture is then washed with H2O (2×15 mL) and brine (10 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product is chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge
  5. washeluting with a gradient of MeOH/CH2Cl2 (0.5/99.5-2/98)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8f79fd1ec183403780bef650daa2bed4
Source dataset
uspto-grants-2005_12
Patent number
US06972286B2

Reaction notes

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