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tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate → 4-[3-(Tert-butyl-dimethyl-silanyloxy)benzoyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 445030
ノート
印刷プレビュー

反応式

HRID 445030 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[Li]CCCC.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([C:34](=[O:39])N(OC)C)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]>C1COCC1>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([C:34](=[O:39])[C:2]2[CH:15]=[CH:14][CH:13]=[C:4]([O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7])[CH:3]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 11254705(3-Bromophenoxy)(tert-butyl)dimethylsilaneHCID 178418339Butyllithium

生成物 1

HCID 697908934-[3-(Tert-butyl-dimethyl-silanyloxy)benzoyl]-piperidine-1-carboxylic acid tert-butyl ester収率 57.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran
溶媒
2 回

実験手順

To the solution of (3-bromophenoxy)-tert-butyldimethylsilane (from Example 5, 6.12 g) in THF (120 mL) at −75° C. was slowly added nBuLi (9.37 mL of 2.5 M solution) under nitrogen. After 15 minutes, the solution of 4-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylic acid tert-butyl ester (5.80 g) in THF (10 mL) was dropwise added. The reaction was stirred under nitrogen overnight while it warmed to room temperature. The reaction was quenched by slow addition of aqueous NH4Cl solution (80 mL). The resulting mixture was extracted by EtOAc (120 mL). The organic layer was washed by water (80 mL×3) and brine (80 mL×1), dried by Na2SO4 and concentrated to give crude product (9.13 g), which was purified to afford pure 4-[3-(tert-butyl-dimethylsilanyloxy)benzoyl]piperidine-1-carboxylic acid tert-butyl ester (5.12 g; 57%). 1H NMR (600 MHz, DMSO-d6) δ 7.60 (d, 1H, J=8.0 Hz), 7.41 (dd, 1H, J=8.0, 8.0 Hz), 7.32 (m, 1H), 7.11 (dd, 1H, J=8.0, 2.5 Hz), 3.94 (m, 2H), 3.57 (m, 1H), 2.90 (bs, 2H), 1.72 (m, 2H), 1.38 (s, 9H), 1.37 (m, 2H), 0.94 (s, 9H), 0.19 (s, 6H).

後処理

  1. customat −75° C.
  2. customThe reaction was quenched by slow addition of aqueous NH4Cl solution (80 mL)
  3. extractionThe resulting mixture was extracted by EtOAc (120 mL)
  4. washThe organic layer was washed by water (80 mL×3) and brine (80 mL×1)
  5. dry with materialdried by Na2SO4
  6. concentrationconcentrated
  7. customto give crude product (9.13 g), which
  8. customwas purified

出典と根拠

ORDレコード
ord-6cb755fa27a94df3959efad826a0bca8
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08476280B2

反応ノート

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