Methanol → HCID 68212573, compound
Reaction equation
C([Si](C)(C)[O:6][C@@H:7]1[CH2:12][CH2:11][C@H:10]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:23][CH2:22][C:21]4([CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[C:20]3=[O:29])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].CO>C1COCC1.C(Cl)Cl.CCOC(C)=O>[OH:6][CH:7]1[CH2:8][CH2:9][CH:10]([C:13]2[CH:14]=[CH:15][C:16]([N:19]3[CH2:23][CH2:22][C:21]4([CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[C:20]3=[O:29])=[CH:17][CH:18]=2)[CH2:11][CH2:12]1Participants
Conditions
- Temperature
- 60 °C
Procedure
Cis-2-{4-[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-phenyl}-8-oxa-2-aza-spiro[4.5]decan-1-one (intermediate 19) (500 mg, 1.13 mmol) was dissolved in THF (10 mL). To this solution at rt was added TBAF (1 M in THF) (2.9 mL, 2.9 mmol, 2.5 equiv.). The reaction mixture was then heated to 60° C. (external) for 5 h. After the reaction was complete (TLC, 5% MeOH in DCM), the reaction was diluted with EtOAc (5 mL), quenched with NH4Cl (aq. saturated, 5 mL). The two layers were separated and the aq. layer was extracted with EtOAc (2×15 mL). The EtOAc solution was combined, washed with NH4Cl aq, NaHCO3 aq, and brine (10 mL each), sequentially, and dried over K2CO3, filtered and concentrated. The crude product was purified on a silica gel column, eluted with 5% MeOH in DCM to afford 0.375 g (100% yield) of the title compound as a white solid.
Workup
- customquenched with NH4Cl (aq. saturated, 5 mL)
- customThe two layers were separated
- extractionthe aq. layer was extracted with EtOAc (2×15 mL)
- washwashed with NH4Cl aq, NaHCO3 aq, and brine (10 mL each)
- dry with materialsequentially, and dried over K2CO3
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified on a silica gel column
- washeluted with 5% MeOH in DCM
Sources & evidence
- ORD record
- ord-fb92cca2e3c74e06b31551bc4d786639
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08735385B2
Reaction notes
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