Ethanol → HCID 58732735, compound

HRID 553007Notes

Reaction equation

HRID 553007 reaction equation
C([O:3][C:4](=[O:40])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C@@H:20]([C:27](=[O:38])[N:28]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)[CH2:29][CH3:30])[CH2:19][C@@H:18]2[CH3:39])=[O:16])=[CH:11][CH:10]=1)C.[OH-].[Li+].C(O)C>O1CCCC1.O>[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([N:28]([CH2:29][CH3:30])[C:27]([C@@H:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:17]([C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:40])=[O:3])=[CH:14][CH:13]=3)=[O:16])[C@@H:18]([CH3:39])[CH2:19]2)=[O:38])=[CH:32][CH:33]=1.[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([N:28]([CH2:29][CH3:30])[C:27]([C@H:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:17]([C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:40])=[O:3])=[CH:14][CH:13]=3)=[O:16])[C@@H:18]([CH3:39])[CH2:19]2)=[O:38])=[CH:32][CH:33]=1

Participants

7

Reactant 3

HCID 702EthanolHCID 3939Lithium HydroxideHCID 58732756HCID 58732756, compound

Product 2

HCID 58732735HCID 58732735, compoundHCID 86608600HCID 86608600, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(±)-trans-4-(4-{4-[(4-Chloro-phenyl)-ethyl-carbamoyl]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid ethyl ester (520 mg, 0.923 mmol) was dissolved in tetrahydrofuran (15 mL). A solution of lithium hydroxide (77 mg, 1.8 mmol) in water (5 mL) was added. Ethanol was added until the reaction was homogeneous. The resulting solution was allowed to stir at room temperature overnight. The solution was concentrated to remove ethanol and tetrahydrofuran. The resulting aqueous mixture was acidified with concentrated hydrochloric acid until pH=1-2. The heterogeneous mixture was immediately extracted with ethyl acetate (2×75 mL). The extracts were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was a mixture of cis and trans isomers. A portion of the crude residue was purified by HPLC to afford pure (±)-trans-4-(4-{4-[(4-chloro-phenyl)-ethyl-carbamoyl]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid and pure (±)-cis-4-(4-{4-[(4-chloro-phenyl)-ethyl-carbamoyl]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid. The remainder of the mixture was used without further purification in subsequent reactions. Data for the trans isomer: 1H-NMR (CD3OD) δ: 0.97 (d, 3H), 1.12 (t, 3H), 4.73 (ddd, 1H), 2.00-2.13 (m, 2H), 2.47-2.58 (m, 3H), 3.61-3.99 (m, 5H), 5.02-5.12 (m, 1H), 6.44 (d, 1H), 6.68-6.74 (m, 2H), 6.75-6.83 (m, 2H), 6.85-6.92 (m, 1H), 7.17-7.25 (m, 3H), 7.42-7.51 (m, 4H). MS m/z: 535 (M+1).

Workup

  1. concentrationThe solution was concentrated
  2. customto remove ethanol and tetrahydrofuran
  3. extractionThe heterogeneous mixture was immediately extracted with ethyl acetate (2×75 mL)
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additiona mixture of cis and trans isomers
  9. customA portion of the crude residue was purified by HPLC

Sources & evidence

ORD record
ord-38b6f92830b842a4b0263d68ebb91299
Source dataset
uspto-grants-2011_05
Patent number
US07951950B2

Reaction notes

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