Methanol → 4-(7-Methoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester
Reaction equation
[OH-:1].[K+].COC([C:7]1([C:20]2[C:29]3[C:24](=[CH:25][C:26](Cl)=[CH:27][CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=O.[CH3:31]O>>[C:16]([O:15][C:13]([N:10]1[CH2:9][CH2:8][CH:7]([C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:1][CH3:31])=[CH:27][CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH2:12][CH2:11]1)=[O:14])([CH3:17])([CH3:19])[CH3:18]Participants
4
Conditions
- Temperature
- 100 °C
Procedure
Solid KOH (224 mg, 4 mmol) was added to a solution of 4-(7-chloro-quinazolin-4-yl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (3a; 41 mg, 0.1 mmol), prepared as described in Example 3, in anhydrous MeOH (1 mL). The mixture was stirred at 100° C. for 3 h. It was then cooled to rt and concentrated in vacuo. The residue was dissolved in DCM and washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to obtain crude 4-(7-methoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (4a). This was dissolved in 2 mL of 3M HCl/MeOH was stirred at rt for 1 h and then concentrated in vacuo to obtain crude 4-(7-methoxy-quinazolin-4-yl)-piperidine (4b) as a di-HCl salt.
Workup
- customprepared
- temperatureIt was then cooled to rt
- concentrationconcentrated in vacuo
- dissolutionThe residue was dissolved in DCM
- washwashed with water, brine
- dry with materialdried over anhydrous MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-72696abb83014963897ac9905446e7e9
- Source dataset
- uspto-grants-2010_11
- Patent number
- US07825244B2
Reaction notes
Loading…