Hydrochloric Acid → Mirabegron

HRID 1392375Notes

Reaction equation

HRID 1392375 reaction equation
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH:11][CH2:12][C@@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[OH:14])=[CH:5][CH:4]=1.[NH2:21][C:22]1[S:23][CH:24]=[C:25]([CH2:27][C:28](O)=[O:29])[N:26]=1.Cl.Cl.CN(C)CCCN=C=NCC.[OH-].[Na+]>O>[NH2:21][C:22]1[S:23][CH:24]=[C:25]([CH2:27][C:28]([NH:2][C:3]2[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][NH:11][CH2:12][C@H:13]([OH:14])[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:7][CH:8]=2)=[O:29])[N:26]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 34665(2-Amino-1,3-thiazol-4-yl)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 529530072-((4-Aminophenethyl)amino)-1-phenylethanol hydrochloride, (R)-

Product 1

HCID 9865528Mirabegron

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a mixed solution of 13.50 kg of (R)-2-[[2-(4-aminophenyl) ethyl]amino]-1-phenylethanol monohydrochloride, 7.29 kg of 2-aminothiazol-4-yl-acetic acid, 4.46 kg of concentrated hydrochloric acid and 270 L of water, 9.73 kg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride (EDC) was added at 15° C., and the mixture was stirred for one hour. A mixed solution of 4.10 kg of sodium hydroxide and 110 L of water was dropped in the reaction solution, thereby undergoing crystallization. A generated crystal was collected by filtration and washed with water to obtain 26.2 kg of a wet cake of the β-form crystal of (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetanilide. This crystal was used for recrystallization as it was in the wet state.

Workup

  1. customcrystallization
  2. filtrationA generated crystal was collected by filtration
  3. washwashed with water

Sources & evidence

ORD record
ord-7321fc6bd2354790823bd707d4a288b5
Source dataset
uspto-grants-2008_03
Patent number
US07342117B2

Reaction notes

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