Cesium carbonate → 3-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-azetidine-1-carboxylic acid tert-butyl ester

HRID 1890435Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][C:10]2([O:12][CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:14][O:15][C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[CH:21][C:22](=[O:26])[NH:23]2)=[CH:18][CH:17]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][C:10]([OH:12])([CH2:11][N:23]2[C:24]3[C:19](=[CH:18][CH:17]=[C:16]([O:15][CH3:14])[CH:25]=3)[CH:20]=[CH:21][C:22]2=[O:26])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of oxa-5-azaspiro[2.3]hexane-5-carboxylic acid tert-butyl ester (69 mg; prepared according to WO 2007/044515) in DMF (1 mL) was added to a suspension of 7-methoxy-2(1H)-quinolinone (60 mg; commercial) and Cs2CO3 (223 mg, 2 eq.) in DMF (2 mL). The reaction mixture was stirred at 80° C. for 10 days. The solvent was removed under reduced pressure and the residue was partitioned between water and EA. The aq. layer was extracted with EA. The combined org. layers were dried over Na2SO4, filtered, evaporated and purified by CC (DCM-MeOH 19:1 to 9:1) to afford the title intermediate as a yellow oil (12 mg, 10% yield).

Workup

customThe solvent was removed under reduced pressure
customthe residue was partitioned between water and EA
extractionThe aq. layer was extracted with EA
dry with materiallayers were dried over Na2SO4
filtrationfiltered
customevaporated
custompurified by CC (DCM-MeOH 19:1 to 9:1)

Sources & evidence

ORD record: ord-e5b6392ff8aa45278257399ba9c1bdd5
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507478B2

Reaction notes

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