tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-(4-methylthiazol-5-yl)piperazine-1-carboxylate

HRID 1775325ノート

反応式

HRID 1775325 の反応式
Br[C:2]1[S:6][CH:5]=[N:4][C:3]=1[CH3:7].[C:8]([N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].CC(C)([O-])C.[Na+]>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C(OC)=CC=C(OC)C=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[CH3:7][C:3]1[N:4]=[CH:5][S:6][C:2]=1[N:18]1[CH2:17][CH2:16][N:15]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:20][CH2:19]1

参加物

8

反応物 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 150209975-Bromo-4-methyl-1,3-thiazoleHCID 23676156Sodium t-butoxide

生成物 1

HCID 89825959tert-Butyl 4-(4-methylthiazol-5-yl)piperazine-1-carboxylate収率 207.6%

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 25112535Brettphos触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
70 °C

実験手順

A solution of 5-bromo-4-methylthiazole (454 mg, 2.55 mmol), N-Boc-piperazine (940 mg, 5.05 mmol), sodium tert-butoxide (492 mg, 5.12 mmol) and dicyclohexyl-[3,6-dimethoxy-2-(2,4,6-thisopropylphenyl)phenyl]phosphane (BrettPhos, 64.9 mg, 0.121 mmol) in anhydrous 1,4-dioxane (9 mL) was flushed with argon for 3 min. Tris(dibenzylideneacetone)dipalladium(0) (106 mg, 0.116 mmol) was added and the mixture was heated in a sealed flask to 70° C. for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc, filtered through kieselguhr and the filtrate was concentrated under reduced pressure to yield 1.5 g of a brown oil which was purified by flash chromatography (silica, gradient of 0.5 to 3% methanol in dichloromethane). 267 mg of a light-yellow oil were obtained (0.942 mmol), 37%). MS (ESI) m/z=284.2 [M+1]+.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through kieselguhr
  3. concentrationthe filtrate was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-596f38200ba849fc999a56d077cf684e
出典データセット
uspto-grants-2016_02
特許番号
US09260441B2

反応ノート

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