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1,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate → tert-butyl (2S)-4-[(4-amino-2-methylphenyl)methyl]-2-methylpiperazine-1-carboxylate

HRID 644732
ノート
印刷プレビュー

反応式

HRID 644732 の反応式
C([NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@@H:14]([CH3:25])[CH2:13]2)=[C:7]([CH3:26])[CH:6]=1)(=O)C>[OH-].[K+].CO>[NH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[C@@H:14]([CH3:25])[CH2:13]2)=[C:7]([CH3:26])[CH:6]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 1

HCID 592621441,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate

生成物 1

HCID 59262126tert-butyl (2S)-4-[(4-amino-2-methylphenyl)methyl]-2-methylpiperazine-1-carboxylate収率 49.9%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 14797Potassium Hydroxide溶媒

反応条件

温度
130 °C

実験手順

1,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate (D79) (497 mg, 1.4 mmol) in KOH (1M aq soln., 5 mL) and methanol (5 mL) was heated to 140° C. for 1 h in a microwave reactor. The reaction mixture was diluted with methanol (5 mL) and heated for a total of 4 h 55 minutes at 130° C. in the microwave. The reaction mixture was concentrated to remove the methanol and partitioned between DCM and water. The organic layer was dried and concentrated to give the crude product which was purified by chromatography. Elution with 0-100% diethyl ether/petroleum ether followed by a column flush with 10% (2M NH3 in methanol) in DCM yielded the title compound as a yellow oil (223 mg). δH (CDCl3, 400 MHz) 6.97 (1H, d), 6.52 (1H, d), 6.46 (1H, dd), 4.17 (1H, br.s), 3.76 (1H, d), 3.57 (2H, br.s), 3.29 (2H, m), 3.01 (1H, td), 2.70 (1H, d), 2.56 (1H, d), 2.30 (3H, s), 2.10 (1H, dd), 1.90 (1H, m), 1.45 (9H, s), 1.18 (3H, d). MS (AP+): MNa+ 342.3 (MNa+), no molecular ion (MH+) observed.

後処理

  1. concentrationThe reaction mixture was concentrated
  2. customto remove the methanol
  3. custompartitioned between DCM and water
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customwas purified by chromatography
  8. washElution with 0-100% diethyl ether/petroleum ether
  9. customflush with 10% (2M NH3 in methanol) in DCM

出典と根拠

ORDレコード
ord-bb4b6e1e58cc4f54a97fa038f339865c
出典データセット
uspto-grants-2010_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07700599B2

反応ノート

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