Hydrochloric Acid → HCID 66955026, compound
Reaction equation
FC1C=C([C@H]2N(CC(OCC)=O)[C:17](=[O:25])[C:12]3([CH2:16][CH2:15][CH2:14][CH2:13]3)[NH:11]C2)C=C(F)C=1.[F:26][C:27]1[CH:28]=[C:29]([CH:34]=[C:35]([F:37])[CH:36]=1)[C:30](=[O:33])[CH2:31]Br.Cl.CN([CH:42]=[O:43])C>>[F:26][C:27]1[CH:28]=[C:29]([C:30](=[O:33])[CH2:31][NH:11][C:12]2([C:17]([O:43][CH3:42])=[O:25])[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:34]=[C:35]([F:37])[CH:36]=1Participants
Procedure
A mixture of methyl 1-aminocyclopentanecarboxylate hydrochloride (10.0 g, 55.7 mmol, described in Intermediate 25), 3,5-difluorophenacyl bromide (14.4 g, 61.2 mmol), and Na3PO4 (22.8 g, 139 mmol) in DMF (100 mL) was stirred at ambient temperature for 3.5 h. The reaction mixture was acidified with 1 N aqueous HCl and the mixture was extracted with EtOAc (200 mL) and this organic extract was discarded. The aqueous layer was adjusted to pH 8-9 by addition of saturated aqueous NaHCO3 and the mixture was extracted with EtOAc (3×250 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc-90:10 to 50:50, to give the title compound. MS: m/z=298 (M+1).
Workup
- extractionthe mixture was extracted with EtOAc (200 mL)
- extractionthis organic extract
- additionThe aqueous layer was adjusted to pH 8-9 by addition of saturated aqueous NaHCO3
- extractionthe mixture was extracted with EtOAc (3×250 mL)
- washThe combined organic layers were washed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was purified by silica gel chromatography
- washeluting with a gradient of hexane
Sources & evidence
- ORD record
- ord-14643fd6ba974977982b380feb140a06
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07625901B2
Reaction notes
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