Hydrochloric Acid → Carbonic Acid

HRID 604184Notes

Reaction equation

HRID 604184 reaction equation
[F:1][C:2]([F:53])([F:52])[C:3]1[CH:4]=[C:5]([CH:45]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:47]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:39]=[C:38]([CH:40]([CH3:42])[CH3:41])[CH:37]=[CH:36][C:35]=1[O:43][CH3:44])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20]CC)=[O:19])=[CH:10][CH:9]=1.[OH-:54].[Na+].Cl.C(Cl)Cl>C(O)C.O1CCCC1>[C:18](=[O:19])([OH:54])[OH:20].[F:51][C:48]([F:49])([F:50])[C:46]1[CH:45]=[C:5]([CH:4]=[C:3]([C:2]([F:53])([F:52])[F:1])[CH:47]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:32])([F:33])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:39]=[C:38]([CH:40]([CH3:41])[CH3:42])[CH:37]=[CH:36][C:35]=1[O:43][CH3:44])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 86626915HCID 86626915, compound

Product 2

HCID 767Carbonic AcidHCID 23641809HCID 23641809, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 4-{6-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyridin-3-yloxy}-butyrate (150 mg) is dissolved in a mixed solvent of ethanol (1 ml) and tetrahydrofuran (2 ml) and thereto is added a 2N-aqueous sodium hydroxide solution (0.3 ml) and the mixture is stirred at 50° C. for 3 hours and 20 minutes. The reaction solution is cooled to room temperature and neutralized with a 2N-hydrochloric acid (0.3 ml), and thereto are added methylene chloride and a saturated brine and the mixture is separated, and the organic layer is concentrated under reduced pressure. The resulting residue is purified by LCMS (column: CAPCELPACK MG2 C18, eluate: a 10 μM aqueous carbonic acid solution/acetonitrile=55/45→40/60) to give 4-{6-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyridin-3-yloxy}-butyric acid (31.4 mg). The resulting carboxylic acid is dissolved in ethanol (1 ml) and thereto is added a 2N-aqueous sodium hydroxide solution (42 μl) and the reaction solution is concentrated under reduced pressure to give 4-{6-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyridin-3-yloxy}-butyric acid sodium salt (30.6 mg). MS (m/z): 727 [M−Na]−

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. customa saturated brine and the mixture is separated
  3. concentrationthe organic layer is concentrated under reduced pressure
  4. customThe resulting residue is purified by LCMS (column

Sources & evidence

ORD record
ord-8e540ad8ca24484cb068cc5c0c7303ba
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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