Acetic Acid → tert-Butyl 4-(4-fluoro-2-(2-hydroxyethylthio)-5-nitrophenylamino)piperidine-1-carboxylate

HRID 424594ノート

反応式

HRID 424594 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([F:11])=[CH:4][C:3]=1[S:12][CH2:13][CH2:14][OH:15].O=[C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[F:11][C:5]1[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]([NH:1][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[C:3]([S:12][CH2:13][CH2:14][OH:15])[CH:4]=1

参加物

6

反応物 4

HCID 176Acetic AcidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate3 回HCID 5049666Sodium triacetoxyborohydride3 回HCID 591440992-(2-Amino-5-fluoro-4-nitrophenylthio)ethanol

生成物 1

HCID 59144085tert-Butyl 4-(4-fluoro-2-(2-hydroxyethylthio)-5-nitrophenylamino)piperidine-1-carboxylate収率 91.4%

試薬・触媒・溶媒 1

HCID 63651,1-Dichloroethane溶媒

実験手順

To a stirred solution of 2-(2-amino-5-fluoro-4-nitrophenylthio)ethanol (434 mg, 1.869 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (372 mg, 1.869 mmol) in dichloroethane (10 mL) and acetic acid (0.321 mL, 5.61 mmol) was added sodium triacetoxyborohydride (594 mg, 2.80 mmol). The resulting mixture was stirred at room temperature. After 1 hour, additional tert-butyl 4-oxopiperidine-1-carboxylate (372 mg, 1.869 mmol) was added, followed by additional sodium triacetoxyborohydride (594 mg, 2.80 mmol). After a further 3 hours, more tert-butyl 4-oxopiperidine-1-carboxylate (372 mg, 1.869 mmol) was added followed by more sodium triacetoxyborohydride (594 mg, 2.80 mmol). The reaction mixture was stirred overnight. The mixture was then quenched with 1 N NaOH (10 mL), water (20 mL), and saturated sodium carbonate (20 mL). The organic products were then extracted with dichloromethane (3×20 mL). The combined organics were dried, filtered, concentrated, and then chromatographed using 1:3 ethyl acetate:hexanes on silica gel to give the desired product (710 mg, 91%). 1H NMR (DMSO-d6) δ 7.45 (d, J=12.0 Hz, 1H), 7.23 (d, J=6.6 Hz, 1H), 5.08 (t, J=5.4 Hz, 1H), 5.02 (d, J=8.1 Hz, 1H), 3.96-3.84 (m, 2H), 3.69-3.55 (m, 5H), 2.99-2.83 (m, 2H), 1.92-1.83 (m, 2H), 1.45-1.18 (m, 11H); ESI-MS (m/z, %): 360 (100), 128 (30).

後処理

  1. waitAfter a further 3 hours
  2. stirringThe reaction mixture was stirred overnight
  3. customThe mixture was then quenched with 1 N NaOH (10 mL), water (20 mL), and saturated sodium carbonate (20 mL)
  4. extractionThe organic products were then extracted with dichloromethane (3×20 mL)
  5. customThe combined organics were dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed

出典と根拠

ORDレコード
ord-099421b9e7eb4b4ab814bb7de8a996ef
出典データセット
uspto-grants-2012_01
特許番号
US08106043B2

反応ノート

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