Ethanol → Rifaximin

HRID 409628Notes

Reaction equation

HRID 409628 reaction equation
[CH3:1][C@@H:2]1[C@H:36]([OH:37])[C@@H:35]([CH3:38])[C@@H:34]([OH:39])[C@@H:33]([CH3:40])[C@H:32]([O:41][C:42]([CH3:44])=[O:43])[C@H:31]([CH3:45])[C@@H:30]([O:46][CH3:47])[CH:29]=[CH:28][O:27][C@:24]2([CH3:48])[C:25](=[O:26])[C:14]3[C:15]([O:23]2)=[C:16]([CH3:22])[C:17]([OH:21])=[C:18]2[C:19](=[O:20])[C:10](=[CH:11][C:12]4(OC(=O)CO4)[C:13]=32)[NH:9][C:7](=[O:8])[C:6]([CH3:54])=[CH:5][CH:4]=[CH:3]1.C(O)C.[NH2:58][C:59]1[CH:64]=[C:63]([CH3:65])[CH:62]=[CH:61][N:60]=1.O=C1O[C@H]([C@H](CO)O)C(O)=C1O>Cl.O>[CH3:65][C:63]1[CH:62]=[CH:61][N:60]2[C:11]3[C:10]4[NH:9][C:7](=[O:8])[C:6]([CH3:54])=[CH:5][CH:4]=[CH:3][C@H:2]([CH3:1])[C@H:36]([OH:37])[C@@H:35]([CH3:38])[C@@H:34]([OH:39])[C@@H:33]([CH3:40])[C@H:32]([O:41][C:42]([CH3:44])=[O:43])[C@H:31]([CH3:45])[C@@H:30]([O:46][CH3:47])[CH:29]=[CH:28][O:27][C@:24]5([CH3:48])[C:25](=[O:26])[C:14]6=[C:15]([O:23]5)[C:16]([CH3:22])=[C:17]([OH:21])[C:18](=[C:13]6[C:12]=3[N:58]=[C:59]2[CH:64]=1)[C:19]=4[OH:20]

Participants

7

Reactant 4

HCID 702EthanolHCID 15332-Amino-4-methylpyridineHCID 5280468Rifamycin, 4-O-(carboxymethyl)-1-deoxy-1,4-dihydro-4-hydroxy-1-oxo-, gamma-lactoneHCID 54670067L-Ascorbic Acid

Product 1

HCID 6436173Rifaximin

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
27.5 °C

Procedure

Rifamycin O (50 g) and 76 ml of ethanol were stirred in a RBF at 20-30° C., for 15 minutes, DM water (100 ml) and 21.5 g of 2-Amino-4-picoline were added and stirred for 15 minutes at 25-30° C. The reaction mass was heated to 47° C. and stirred for 4-5 hours. Reaction mass was cooled to 20° C. and a solution of 1.32 g of ascorbic acid in 10 ml of concentrated HCl and 7.1 ml of DM water was added into it in 30 minutes. The reaction mixture was stirred for 30 minutes at 20° C.; ˜8.75 ml of concentrated HCl was added into it to adjust the pH to 1.5-2.0 and further stirred. The crude was isolated by filtration, washed with 100 ml of 1:1 Ethanol and water mixture. The Crude was pulped with DM water until the pH of filtrate is neutral, dried for 10-12 hours at 70° C. until the moisture content was <5.0%.

Workup

  1. temperatureThe reaction mass was heated to 47° C.
  2. stirringstirred for 4-5 hours
  3. customReaction mass
  4. temperaturewas cooled to 20° C.
  5. stirringThe reaction mixture was stirred for 30 minutes at 20° C.
  6. stirringfurther stirred
  7. customThe crude was isolated by filtration
  8. washwashed with 100 ml of 1:1 Ethanol and water mixture
  9. customdried for 10-12 hours at 70° C. until the moisture content

Sources & evidence

ORD record
ord-abce733687f54a1f84d92fcdafb7159d
Source dataset
uspto-grants-2014_06
Patent number
US08759513B2

Reaction notes

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