Tetrahydrofuran → HCID 86651622, compound

HRID 472716Notes

Reaction equation

[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:40])[C:16]([N:18]2[CH2:31][CH2:30][C@@:21]3([NH:25][CH2:24][CH2:23][CH:22]3[C:26]([O:28]C)=[O:27])[CH2:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[CH3:39])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O[Li:44].O.O1CCCC1>CO.O>[F:42][C:2]([F:1])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:40])[C:16]([N:18]2[CH2:31][CH2:30][C@@:21]3([NH:25][CH2:24][CH2:23][C@@H:22]3[C:26]([O-:28])=[O:27])[CH2:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[CH3:39])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1.[Li+:44]

Participants

Conditions

Temperature: 50 °C

Procedure

Methyl (5R,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-4-carboxylate (Intermediate 41, 12 mg, 0.020 mmol) was dissolved in Methanol (0.3 ml) and Water (0.3 ml). To the mixture was added LiOH.H2O (0.918 mg, 0.022 mmol) and the reaction mixture was left stirring overnight at 50° C. To the solution was added Tetrahydrofuran (THF) (0.3 ml) and it was heated at 70° C. for 1 more hour. The solvent was removed in vacuo obtaining the title compound (11.2 mg, 0.019 mmol, 96% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 7.98 (s, 1H) 7.69 (s, 2H) 7.07-7.15 (m, 1H) 6.84-6.91 (m, 1H) 6.69-6.79 (m, 1H) 5.25-5.38 (m, 1H) 4.43 (d, 1H) 2.98-3.23 (m, 2H) 2.69 (s, 3H) 2.60-2.92 (m, 2H) 2.31 (s, 3H) 1.56-2.04 (m, 5H) 1.48 (d, 3H) 1.40-1.54 (m, 1H) 1.33 (d, 1H). Stereochemistry consistent with the following data:

Workup

waitthe reaction mixture was left
temperaturewas heated at 70° C. for 1 more hour
customThe solvent was removed in vacuo

Sources & evidence

ORD record: ord-2a930d6359814cd8a316f1b457b9977d
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633214B2

Reaction notes

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