Hydrochloric Acid → Solabegron

HRID 1624204Notes

Reaction equation

HRID 1624204 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:29])[CH2:9][NH:10][CH2:11][CH2:12][NH:13][C:14]2[CH:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([OH:28])=[O:27])[CH:21]=3)[CH:17]=[CH:18][CH:19]=2)[CH:5]=[CH:6][CH:7]=1.O.[OH-].[Li+].COC(C1C=C(C2C=CC=C(NCCNC[C@@H](C3C=CC=C(Cl)C=3)O)C=2)C=CC=1)=O.Cl>O.C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:29])[CH2:9][NH:10][CH2:11][CH2:12][NH:13][C:14]2[CH:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([OH:28])=[O:27])[CH:21]=3)[CH:17]=[CH:18][CH:19]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 6433124HCID 6433124, compoundHCID 9845280HCID 9845280, compound

Product 1

HCID 9887812SolabegronYield 41.36%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

3′-(2 (2 (3 chlorophenyl)-2-hydroxyethylamino)ethylamino)biphenyl-3-carboxylic acid (solabegron): A solution of 10% lithium hydroxide monohydrate in water (2 mL) was added to a solution of (R)-3′-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]ethylamino}-biphenyl-3-carboxylic acid methyl ester (50 mg, 0.12 mmol, 1.00 equiv) in ethanol (4 mL). The solution was stirred at ambient temperature for about 16 hours, and then the pH value of the solution was adjusted to 7-8 with concentrated hydrogen chloride. After concentrating the solution in vacuo, the resulting crude residue was purified by prep-HPLC to give the title product of as a white solid (20 mg; yield=41.36%). LC-MS: m/z=411 (MH)+. Retention time: 1.69 minute. [α]20.4D −20° (c=0.075, MeOH). [α]=−20° (c=0.075 g/100 ml in methanol, T=20.4). 1H NMR (300 MHz, CD3OD) δ: 8.22 (s, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.47 (s, 1H), 7.29-7.38 (m, 4H), 7.20 (t, J=8.1 Hz, 1H), 6.97 (m, 2H), 6.68 (d, J=1.5 Hz, 1H), 5.00 (m, 1H), 3.56 (t, J=6.0 Hz, 2H), 3.23-3.33 (m, 3H), 3.12 (m, 1H).

Workup

  1. concentrationAfter concentrating the solution in vacuo
  2. customthe resulting crude residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-9e1bc82d065d4a7f94ced999a0784e6e
Source dataset
uspto-grants-2014_07
Patent number
US08778998B2

Reaction notes

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