Sodium Hydroxide → 4-[1-(2-Trimethylsilanylethanesulfonyl)piperidin-4-yloxy]benzonitrile

HRID 529978

反応式

HRID 529978 の反応式
[CH3:1][Si:2]([CH3:10])([CH3:9])[CH2:3][CH2:4][S:5](Cl)(=[O:7])=[O:6].Cl.[NH:12]1[CH2:17][CH2:16][CH:15]([O:18][C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[CH2:14][CH2:13]1.[OH-].[Na+]>C(Cl)Cl>[CH3:1][Si:2]([CH3:10])([CH3:9])[CH2:3][CH2:4][S:5]([N:12]1[CH2:13][CH2:14][CH:15]([O:18][C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[CH2:16][CH2:17]1)(=[O:7])=[O:6]

参加物

5

反応物 3

HCID 14798Sodium HydroxideHCID 98370862-(Trimethylsilyl)ethane-1-sulfonyl chlorideHCID 178322734-(Piperidin-4-yloxy)benzonitrile hydrochloride

生成物 1

HCID 675059384-[1-(2-Trimethylsilanylethanesulfonyl)piperidin-4-yloxy]benzonitrile

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-30 °C

実験手順

Step-3: To a stirred solution of 9.84 g (0.049 mol) of 2-trimethylsilanylethanesulfonyl chloride (SESCl) in DCM (100 mL) cooled to −78° C., was added the step-2 product, 4-(piperidin-4-yloxy)benzonitrile hydrochloride, (9.00 g, 0.038 mol). The mixture was stirred 30 min, warmed to −30° C., and stirred 3 h. To this mixture was added 20 mL of 1N NaOH solution added, and the DCM and aqueous layers partitioned. The aqueous layer was back extracted with DCM (50 mL) and the combined organic layers washed with brine (50 mL), saturated aqueous NaHCO3 (2×30 mL), dried (MgSO4) and concentrated in vacuo. The crude product was repeatedly crystallized from the minimum amount of DCM in hexanes to get the step-3 product, 4-[1-(2-trimethylsilanylethanesulfonyl)piperidin-4-yloxy]benzonitrile, compound B, as a white solid. (12.95 g, 94%): LCMS [MH+] 367, Rt 3.53; 1H NMR (300 MHz, (CD3)2CO-d6) δ 0.80 (s, 9H), 0.97-1.02 (m, 2H), 1.79-1.88 (m, 2H), 2.04-2.15 (m, 2H), 3.28-3.36 (m, 2H), 3.52-3.60 (m, 2H), 4.79 (septet, J=3.9 Hz, 1H), 7.16 (d, J=9.0 Hz, 2H), 7.70 (d, J=9.0 Hz, 2H).

後処理

  1. stirringstirred 3 h
  2. additionadded
  3. customthe DCM and aqueous layers partitioned
  4. extractionThe aqueous layer was back extracted with DCM (50 mL)
  5. washthe combined organic layers washed with brine (50 mL), saturated aqueous NaHCO3 (2×30 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was repeatedly crystallized from the minimum amount of DCM in hexanes

出典と根拠

ORDレコード
ord-1f37416664f141a98aabbdc4a7da4bc6
出典データセット
uspto-grants-2016_05
特許番号
US09351964B2

関連ノート

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