Hydrochloric Acid → HCID 178461147, compound

HRID 2404153

Reaction equation

CS([O:5][C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]([F:15])([F:14])[CH3:13])[CH2:8][CH2:7]1)(=O)=O.O[C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[CH:23]=[C:22]([CH2:27][N:28]1[CH2:31][CH:30]([C:32]([O:34]C)=[O:33])[CH2:29]1)[CH:21]=[CH:20]2.C([O-])([O-])=O.[Cs+].[Cs+].Cl>C(O)(C)(C)C.CC(=O)CC>[F:14][C:12]([C@H:9]1[CH2:10][CH2:11][C@H:6]([O:5][C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[CH:23]=[C:22]([CH2:27][N:28]2[CH2:29][CH:30]([C:32]([OH:34])=[O:33])[CH2:31]2)[CH:21]=[CH:20]3)[CH2:7][CH2:8]1)([F:15])[CH3:13]

Participants

Conditions

Temperature: 110 °C

Procedure

(trans)-4-(1,1-difluoroethyl)cyclohexyl methanesulfonate (WO 2010051030) (0.98 mmol, 236 mg, 1.0 eq.), methyl 1-((6-hydroxynaphthalen-2-yl)methyl)azetidine-3-carboxylate (1.17 mmol, 317 mg, 1.2 mmol) and Cs2CO3 (4.41 mmol, 1.4 g, 4.5 eq.) were dissolved in t-butanol (4 mL) and 2-butanone (2 mL). The mixture was stirred at 110° C. for 16 h. 1 M aq. HCl solution was added to the mixture to adjust pH=6. Then the mixture was extracted with EtOAc. The organic layer was purified by silica gel column chromatography using DCM/CH3OH (10/1) as eluent to give product (7 mg, 1.8%) as a white solid. ESI-MS (M+1)+: 404.1. HPLC: 89.46%. 1H NMR (400 MHz, CD3OD) δ: 7.89 (s, 1H), 7.86-7.81 (m, 2H), 7.46 (dd, 1H), 7.31 (s, 1H), 7.19 (dd, 1H), 4.47 (s, 2H), 4.43-4.41 (m, 1H), 4.21 (d, 4H), 3.45-3.41 (m, 1H), 2.32-2.30 (m, 2H), 2.02-1.99 (m, 2H), 1.64-1.54 (m, 3H), 1.51-1.45 (m, 3H), 1.36-1.28 (m, 2H).

Workup

extractionThen the mixture was extracted with EtOAc
customThe organic layer was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-b99d050f154845788c429b6e448ab345
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802659B2

Linked notes

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