2-Propanol, 2-methyl-, lithium salt (1:1) → Rivaroxaban

HRID 241238Notes

Reaction equation

HRID 241238 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C@H:11]([O:24][C:25](=[O:40])[NH:26][C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][C:34]3=[O:39])=[CH:29][CH:28]=2)[CH2:12]OS(C2C=CC(C)=CC=2)(=O)=O)=[O:8])=[CH:4][CH:3]=1.CC(C)([O-])C.[Li+]>O1CCCC1>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C@@H:11]2[O:24][C:25](=[O:40])[N:26]([C:27]3[CH:28]=[CH:29][C:30]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][C:34]4=[O:39])=[CH:31][CH:32]=3)[CH2:12]2)=[O:8])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 53341423toluene-4-sulfonic acid (S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-2-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyloxy]-propyl ester

Product 1

HCID 9875401RivaroxabanYield 88.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Under an atmosphere of nitrogen a suspension of 1.00 g of toluene-4-sulfonic acid (S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-2-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyloxy]-propyl ester (MW=608.09; 1 eq.) in 25 mL tetrahydrofuran was cooled to 0° C. At this temperature 1.6 mL of a 1M solution of lithium t-butoxide in tetrahydrofuran were added dropwise. After stirring at this temperature for 1 hour the resulting slurry was filtered. The cake was rinsed with 14 mL of tetrahydrofuran and 14 mL of water. The wet product was dried at 30° C. in vacuo to yield 0.63 g (MW=435.89; 1.013 eq.) of the title compound (88.5% of theory).

Workup

  1. filtrationwas filtered
  2. washThe cake was rinsed with 14 mL of tetrahydrofuran and 14 mL of water
  3. customThe wet product was dried at 30° C. in vacuo

Sources & evidence

ORD record
ord-a35e3cb420534529bd37bc630a98ff05
Source dataset
uspto-grants-2014_02
Patent number
US08648189B2

Reaction notes

Loading…