Sodium Carbonate → Rivaroxaban

HRID 898649Notes

Reaction equation

HRID 898649 reaction equation
[NH2:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][C:16]3=[O:21])=[CH:11][CH:10]=2)[CH2:4]1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:28][C:29]1[S:33][C:32]([C:34](Cl)=[O:35])=[CH:31][CH:30]=1>O.CC(C)=O.C1(C)C=CC=CC=1>[Cl:28][C:29]1[S:33][C:32]([C:34]([NH:1][CH2:2][C@@H:3]2[O:7][C:6](=[O:8])[N:5]([C:9]3[CH:14]=[CH:13][C:12]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][C:16]4=[O:21])=[CH:11][CH:10]=3)[CH2:4]2)=[O:35])=[CH:31][CH:30]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 5892235-Chlorothiophene-2-carbonyl ChlorideHCID 11346837(S)-4-(4-(5-(aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one

Product 1

HCID 9875401Rivaroxaban

Reagents, catalysts & solvents 3

HCID 180AcetoneSolvent2×HCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

1160 g of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one (VII) hydrochloride, 350 ml of water and 2.7 l of acetone are successively added to a solution of 464 g of sodium carbonate in 5.95 l of water at 10° C. At 8 to 12° C., 2535 g of 5-chlorothiophene-2-carbonyl chloride (IV) (30% strength solution in toluene) and a further 517 ml of toluene are added. The reaction mixture is then heated to 50° C., 2700 ml of acetone are added, and the mixture is stirred at 50 to 53° C. for a further 30 minutes. After cooling to 26° C., the precipitated reaction product is filtered off with suction and washed with water and acetone.

Workup

  1. temperatureAfter cooling to 26° C.
  2. customthe precipitated reaction product
  3. filtrationis filtered off with suction
  4. washwashed with water and acetone

Sources & evidence

ORD record
ord-e0b4ad3663ed49b9a814340cea904167
Source dataset
uspto-grants-2008_04
Patent number
US07351823B2

Reaction notes

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