Phosgene → methyl (5R)-3-[4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinecarboxylate

HRID 1991297Notes

Reaction equation

HRID 1991297 reaction equation
[O:1]=[S:2]1(=[O:24])[CH2:7][CH2:6][N:5]([C:8]2[C:13]([F:14])=[CH:12][C:11]([NH:15][CH2:16][C@@H:17]([OH:22])[C:18]([O:20][CH3:21])=[O:19])=[CH:10][C:9]=2[F:23])[CH2:4][CH2:3]1.C(N(CC)CC)C.[C:32](Cl)(Cl)=[O:33]>C(Cl)Cl.C1(C)C=CC=CC=1>[O:24]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([C:8]2[C:9]([F:23])=[CH:10][C:11]([N:15]3[CH2:16][C@H:17]([C:18]([O:20][CH3:21])=[O:19])[O:22][C:32]3=[O:33])=[CH:12][C:13]=2[F:14])[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 6371PhosgeneHCID 8471TriethylamineHCID 86610079methyl (2R)-3-{[4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenyl]amino}-2-hydroxypropanoate

Product 1

HCID 68489310methyl (5R)-3-[4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinecarboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of methyl (2R)-3-{[4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenyl]amino}-2-hydroxypropanoate (Step 1, 1.02 g, 2.90 mmol) in CH2Cl2 (25 mL) and triethylamine (1.0 g, 1.5 mL, 10.5 mmol) is cooled to 0° C. and treated with phosgene (1.94 mL of a 20% solution in toluene, 3.6 mmol). After stirring at room temperature for one hour, the reaction mixture is diluted with CH2Cl2 and washed with dilute NaHCO3, saline, and dried (MgSO4), filtered and concentrated. Chromatography on silica gel (10% acetonitrile-dichloromethane) provides the title compound (0.91 g, 83%), MS (m/z): [M+H]+=391; 1H NMR (300 MHz, CDCl3): δ 3.16-3.20 (m, 4H), 3.64 (m, 4H), 3.88 (s, 3H), 4.06-4.11 (m, 1H), 4.23 (t, 1H), 5.06-5.11 (m, 1H), 7.16 (d, 2H).

Workup

  1. washwashed with dilute NaHCO3, saline
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-dbabb24ae365441da9c0a83e4646097c
Source dataset
uspto-grants-2010_01
Patent number
US07645781B2

Reaction notes

Loading…