Hydrochloric Acid → 1-{[1-(2-Methoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid

HRID 719845Notes

Reaction equation

HRID 719845 reaction equation
C([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:21]=3)[CH2:16][N:15]2[C:38](=[O:49])[CH:39]([NH:44][C:45]([O:47][CH3:48])=[O:46])[C:40]([CH3:43])([CH3:42])[CH3:41])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])C.O.[OH-].[Li+].Cl>C1COCC1.CO.O>[CH3:48][O:47][C:45]([NH:44][CH:39]([C:40]([CH3:43])([CH3:42])[CH3:41])[C:38]([N:15]1[CH2:16][CH:17]([O:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=3)[N:23]=[C:22]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH:21]=2)[CH2:18][CH:14]1[C:12]([NH:11][C:6]1([C:4]([OH:5])=[O:3])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:13])=[O:49])=[O:46]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 66670071HCID 66670071, compound

Product 1

HCID 219010671-{[1-(2-Methoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acidYield 69%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-{[1-(2-methoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropane-carboxylic acid ethyl ester (410 mg, 0. 52 mmol) in THF (20 mL), methanol (11.5 mL) and water (3.8 mL) mixture, lithium hydroxide monohydrate (328 mg, 7.82 mmol) was added. The reaction mixture was stirred at rt for overnight. Then it was acidified with 1N HCl solution and concentrated. The residue was extracted with EtOAc twice and the organic layers were combined. Then it was dried (MgSO4) and concentrated to give an off-white solid. (230 mg, 69% yield). 1H NMR (400 MHz, CD3OD) δ 1.02 (s, 9H), 1.43 (dd, J=9.54, 5.14 Hz, 1H), 1.68 (dd, J=8.07, 5.14 Hz, 1H), 2.17 (m, 1H), 2.57 (m, 1H), 2.75 (m, 1H), 3.34 (s, 3H), 4.03 (s, 3H), 4.06 (m, 1H), 4.18 (s, 1H), 4.60–4.70 (m, 2H), 4.88 (m, 1H), 5.08 (dd, J=10.39, 1.59 Hz, 1H), 5.25 (dd, J=17.36, 1.71 Hz, 1H), 5.77–5.87 (m, 2H) 7.38 (dd, J=9.29, 2.20 Hz, 1H), 7.50 (m, 1H), 7.62 (m, 1H), 7.69–7.78 (m, 3H), 8.03–8.07 (m, 2H), 8.36 (d, J=9.20 Hz, 1H). LC-MS (retention time: 2.177 min.), MS m/z 645 (MH+).

Workup

  1. concentrationconcentrated
  2. extractionThe residue was extracted with EtOAc twice
  3. dry with materialThen it was dried (MgSO4)
  4. concentrationconcentrated
  5. customto give an off-white solid

Sources & evidence

ORD record
ord-87e61a73ce004b5b9b67768647a17429
Source dataset
uspto-grants-2006_11
Patent number
US07132504B2

Reaction notes

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