Phosgene → (5R)-3-(8-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-2-oxo-5-oxazolidinecarboxylic acid methyl ester

HRID 1991327Notes

Reaction equation

HRID 1991327 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH3:5][O:6][C:7](=[O:25])[CH:8]([OH:24])[CH2:9][NH:10][C:11]1[CH:12]=[C:13]2[C:18](=[C:19]([F:21])[CH:20]=1)[N:17]([CH3:22])[C:16](=[O:23])[CH2:15][CH2:14]2.C(N(CC)CC)C>ClCCl>[CH3:5][O:6][C:7]([C@@H:8]1[O:24][C:1](=[O:2])[N:10]([C:11]2[CH:12]=[C:13]3[C:18](=[C:19]([F:21])[CH:20]=2)[N:17]([CH3:22])[C:16](=[O:23])[CH2:15][CH2:14]3)[CH2:9]1)=[O:25]

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 8471TriethylamineHCID 684917263-(8-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-ylamino)-2-hydroxypropionic acid methyl ester

Product 1

HCID 68491736(5R)-3-(8-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-2-oxo-5-oxazolidinecarboxylic acid methyl esterYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Phosgene (20% solution in toluene, 4.07 ml, 7.69 mmol) is added dropwise at 0° C. to 3-(8-fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-ylamino)-2-hydroxypropionic acid methyl ester (Step 4, 1.81 g, 6.41 mmol) and triethylamine (2.23 ml, 16.0 mmol) in dichloromethane (25 ml). The mixture is allowed to warm to room temperature and stirred for an additional hour. The reaction is washed with 2N aqueous hydrochloric acid and saline, dried (MgSO4) and evaporated. The residue is purified by flash column chromatography (50% ethyl acetate/hexane) to give the title compound as a white solid (1.71 g, 83%); MS (m/z): [M+H]+=323.

Workup

  1. washThe reaction is washed with 2N aqueous hydrochloric acid and saline
  2. dry with materialdried (MgSO4)
  3. customevaporated
  4. customThe residue is purified by flash column chromatography (50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9f53798f511b4270a35f1f2ed4078801
Source dataset
uspto-grants-2010_01
Patent number
US07645781B2

Reaction notes

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