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

HRID 723885

Reaction equation

HRID 723885 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-e3924cc9ad8740028aa2bcc6e3b1d94d
Source dataset
uspto-grants-2006_11
Patent number
US07141588B2

Linked notes

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