Hydrochloric Acid → Rx-01_423 hydrochloride

HRID 2190696Notes

Reaction equation

HRID 2190696 reaction equation
C(OC(=O)[N:7]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:29][C@H:28]([CH2:30][NH:31][C:32](=[O:34])[CH3:33])[O:27][C:26]3=[O:35])=[CH:21][C:20]=2[F:36])=[CH:15][CH:14]=1)[CH2:8][CH2:9][CH2:10][F:11])(C)(C)C.[ClH:38].O1CCOCC1>C(Cl)Cl>[ClH:38].[F:36][C:20]1[CH:21]=[C:22]([N:25]2[CH2:29][C@H:28]([CH2:30][NH:31][C:32](=[O:34])[CH3:33])[O:27][C:26]2=[O:35])[CH:23]=[CH:24][C:19]=1[C:16]1[CH:17]=[CH:18][C:13]([CH2:12][NH:7][CH2:8][CH2:9][CH2:10][F:11])=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 68540787(5S)-{4'-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2'-fluoro-biphenyl-4-ylmethyl}-(3-fluoro-propyl)-carbamic acid tert-butyl ester

Product 1

HCID 11293964Rx-01_423 hydrochlorideYield 95.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of BOC-amine 121 (15.65 g, 30.3 mmol) in CH2Cl2 (30 mL) was treated with a solution of 4 N hydrogen chloride in 1,4-dioxane (37.5 mL, 150.0 mmol, 5.0 equiv) at room temperature and stirred for 12 h. When TLC and HPLC/MS showed that the reaction was complete, the solvents were removed in vacuo. The residue was suspended in a mixture of acetonitrile (CH3CN, 200 mL) and methanol (MeOH, 50 mL), and the resulting slurry was stirred at room temperature for 1 h. The solids were collected by filtration, washed with 20% MeOH/CH3CN (2×50 mL), and dried in vacuo to afford the desired (5S)—N-(3-{2-fluoro-4′-[(3-fluoro-propylamino)-methyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-ylmethyl)-acetamide mono hydrochloride salt 11 (13.0 g, 95.3% yield) as white crystals. 1H NMR (300 MHz, DMSO-d6) δ 1.90 (s, 3H, COCH3), 2.11-2.20 (m, 2H), 3.10 (m, 2H), 3.50 (t, 2H, J=5.4 Hz), 3.87 (dd, 1H, J=6.4, 9.2 Hz), 4.24 (t, 1H, J=9.1 Hz), 4.27 (s, 2H, ArCH2), 4.54 (t, 1H, J=5.8 Hz), 4.70 (t, 1H, J=5.8 Hz), 4.83 (m, 1H), 7.50 (dd, 1H, J=2.2, 8.6 Hz), 7.65-7.74 (m, 6H, aromatic-H), 8.37 (t, 1H, J=5.8 Hz, NHCOCH3), 9.43 (br. s, 2H, RArN+H2). C22H25F2N3O3HCl, LCMS (EI) m/e 418 (M++H).

Workup

  1. customthe solvents were removed in vacuo
  2. additionThe residue was suspended in a mixture of acetonitrile (CH3CN, 200 mL) and methanol (MeOH, 50 mL)
  3. stirringthe resulting slurry was stirred at room temperature for 1 h
  4. filtrationThe solids were collected by filtration
  5. washwashed with 20% MeOH/CH3CN (2×50 mL)
  6. customdried in vacuo

Sources & evidence

ORD record
ord-31ec7f8083594985a26007ce2fa6e6fa
Source dataset
uspto-grants-2012_12
Patent number
US08324398B2

Reaction notes

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