Tetrahydrofuran → HCID 86651622, compound

HRID 384042Notes

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, 3 H) 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-f3e3969b8f904e619782027100d0cbe6
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367692B2

Reaction notes

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