Potassium Hydroxide → 4-(7-Chloro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1170224ノート

反応式

HRID 1170224 の反応式
[OH-].[K+].COC([C:7]1([C:20]2[C:29]3[C:24](=[CH:25][C:26]([Cl:30])=[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.O1CCOCC1>O>[C:16]([O:15][C:13]([N:10]1[CH2:11][CH2:12][CH:7]([C:20]2[C:29]3[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH2:8][CH2:9]1)=[O:14])([CH3:19])([CH3:17])[CH3:18]

参加物

5

反応物 3

HCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 686934854-(7-Chloro-quinazolin-4-yl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester

生成物 1

HCID 686903624-(7-Chloro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

To a stirred mixture of 4,7-Dichloroquinazoline (800 mg, 4 mmol) and piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (1.2 g, 5.2 mmol), as prepared in Example 1a, in a sealed vial at rt was added drop-wise a 1 M solution of LiHMDS in THF (6 mL, 6 mmol). The mixture was stirred at rt overnight. It was then quenched with aqueous NaH2PO4 and the mixture was extracted with DCM. The DCM layer was drawn off, washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to obtain 2.2 g (>100%) of crude 4-(7-chloro-quinazolin-4-yl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (3a) as a yellow semi-solid which was used as such for the next step. Solid KOH (224 mg, 4 mmol) was added to a suspension 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) in a 1:1 mixture of dioxane and water (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-chloro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (3b). 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-chloro-quinazolin-4-yl)-piperidine (3c) as a di-HCl salt.

後処理

  1. temperatureIt was then cooled to rt
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in DCM
  4. washwashed with water, brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-9ed17b219e4f45dca47ac127f62ed060
出典データセット
uspto-grants-2010_11
特許番号
US07825244B2

反応ノート

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