1,3-Thiazole-2-carbaldehyde → (S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(thiazol-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid

HRID 77604ノート

反応式

HRID 77604 の反応式
[CH:1]1[CH:6]=[C:5]2[CH:7]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:25]([OH:27])=[O:26])[CH2:20][CH2:21][CH2:22][CH2:23][NH2:24])=[O:17])[C:8]3[C:13]([C:4]2=[CH:3][CH:2]=1)=[CH:12][CH:11]=[CH:10][CH:9]=3.Cl.[S:29]1[CH:33]=[CH:32][N:31]=[C:30]1[CH:34]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[C:50]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])(=[O:53])[CH:51]=O>ClCCCl.O>[CH:9]1[C:8]2[CH:7]([CH2:14][O:15][C:16](=[O:17])[NH:18][C@H:19]([C:25]([OH:27])=[O:26])[CH2:20][CH2:21][CH2:22][CH2:23][N:24]([CH2:34][C:30]3[S:29][CH:33]=[CH:32][N:31]=3)[CH2:51][C:50](=[O:53])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[C:5]3[C:4](=[CH:3][CH:2]=[CH:1][CH:6]=3)[C:13]=2[CH:12]=[CH:11][CH:10]=1

参加物

7

反応物 4

HCID 27349031,3-Thiazole-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10986247Tert-butyl 2-oxoacetateHCID 11858928(2S)-6-amino-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acid hydrochloride

生成物 1

HCID 59408631(S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(thiazol-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid収率 21.3%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒

反応条件

温度
0 °C

実験手順

A suspension of Fmoc-Lys-OH. HCl (6.07 g, 15 mmol) and thiazole-2-carbaldehyde (1.697 g, 15 mmol) in DCE (100 mL) was refluxed for 30 min under nitrogen. The reaction mixture was cooled to 0° C., and treated sequentially with NaBH(OAc)3 (7.95 g, 37.5 mmol) and crude tert-butyl glyoxalate (3.53 g). The reaction mixture was stirred at room temperature for overnight and decomposed with water. The reaction mixture was extracted with DCM. The organic layer was dried and concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel to afford (S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(thiazol-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid (1.85 g, 21%). MS (ESI), 580 (M+H)+.

後処理

  1. temperaturewas refluxed for 30 min under nitrogen
  2. extractionThe reaction mixture was extracted with DCM
  3. customThe organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography over silica gel

出典と根拠

ORDレコード
ord-fe2589e59f2f47bbb019c1654b1805ab
出典データセット
uspto-grants-2014_09
特許番号
US08840865B2

反応ノート

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