Triethylamine → Rivaroxaban

HRID 1506827Notes

Reaction equation

HRID 1506827 reaction equation
Cl.[NH2:2][CH2:3][C@@H:4]1[O:8][C:7](=[O:9])[N:6]([C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][C:17]3=[O:22])=[CH:12][CH:11]=2)[CH2:5]1.C(N(CC)CC)C.[Cl:30][C:31]1[S:35][C:34]([C:36](Cl)=[O:37])=[CH:33][CH:32]=1>C(#N)C>[Cl:30][C:31]1[S:35][C:34]([C:36]([NH:2][CH2:3][C@@H:4]2[O:8][C:7](=[O:9])[N:6]([C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][C:17]4=[O:22])=[CH:12][CH:11]=3)[CH2:5]2)=[O:37])=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 5892235-Chlorothiophene-2-carbonyl ChlorideHCID 160370774-(4-((5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl)phenyl)morpholin-3-one hydrochloride

Product 1

HCID 9875401RivaroxabanYield 82.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Under an atmosphere of nitrogen to a suspension of 0.164 g of 4-((S)-5-aminomethyl-2-oxo-oxazolidin-3-yl)-phenyl-morpholin-3-one hydrochloride (MW=327.77; 1 eq.) in 7 mL of acetonitrile were added 0.101 g of triethylamine (MW=101.12; 2.0 eq.). After stirring for 10 min at room temperature, the suspension was cooled to 0° C. and then 0.091 g of 5-chloro-thiophene-2-carbonyl chloride (MW=181.04; 1.0 eq.) were added. After stirring for 80 min at 0° C., the resulting slurry was filtered and the cake washed with 5 mL of acetonitrile and 5 mL of water. After drying in vacuo at 30° C., 0.180 g of the title compound in the form of a white crystalline powder was isolated. Yield=82.7%.

Workup

  1. temperaturethe suspension was cooled to 0° C.
  2. stirringAfter stirring for 80 min at 0° C.
  3. filtrationthe resulting slurry was filtered
  4. washthe cake washed with 5 mL of acetonitrile and 5 mL of water
  5. customAfter drying in vacuo at 30° C.

Sources & evidence

ORD record
ord-e56e9877f2d641248ecb20d25363b6cc
Source dataset
uspto-grants-2015_12
Patent number
US09221771B2

Reaction notes

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