Sodium bis(trimethylsilyl)amide → (R)-tert-butyl 2-(1'-benzyl-2-oxospiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylate

HRID 2190073

反応式

HRID 2190073 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[O:11]=[C:12]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][C:18]=2[C@H:21]2[CH2:25][CH2:24][CH2:23][N:22]2[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[NH:13]1.Cl.[CH2:34]([N:41]([CH2:45][CH2:46]Cl)[CH2:42][CH2:43]Cl)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C1COCC1>[CH2:34]([N:41]1[CH2:45][CH2:46][C:20]2([C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[C@H:21]3[CH2:25][CH2:24][CH2:23][N:22]3[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[NH:13][C:12]2=[O:11])[CH2:43][CH2:42]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

参加物

5

反応物 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 2777881N,N-Bis(2-chloroethyl)benzylamine hydrochlorideHCID 69812735(R)-tert-butyl 2-(2-oxoindolin-4-yl)pyrrolidine-1-carboxylate

生成物 1

HCID 68736950(R)-tert-butyl 2-(1'-benzyl-2-oxospiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylate収率 32.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

NaHMDS (5.0 mL, 5.0 mmol) was added into a solution of (R)-tert-butyl 2-(2-oxoindolin-4-yl)pyrrolidine-1-carboxylate (300 mg, 0.992 mmol) in THF (10 mL) at −78° C. The mixture was stirred for 20 minutes at that temperature. N-benzyl-2-chloro-N-(2-chloroethyl)ethanamine HCl salt (300 mg, 1.12 mmol) was added into the solution at −78° C. The reaction mixture was allowed to warm up to room temperature and was heated to reflux for 12 hours. The reaction was quenched by pouring the reaction mixture into water (10 mL) and was extracted with EtOAc (100 mL). The organic layer was washed with brine, dried with Na2SO4, filtered and concentrated. The residue was purified with flash chromatography to afford the product (R)-tert-butyl 2-(1′-benzyl-2-oxospiro[indoline-3,4′-piperidine]-4-yl)pyrrolidine-1-carboxylate (150 mg, 0.325 mmol, 32.8%) as a solid. 1H NMR (CDCl3, 400 MHz) δ 7.20-7.45 (m, 6H), 7.10 (t, 1H), 6.80 (d, 1H), 6.60-6.70 (m, 1H), 5.40-5.80 (m, 1H), 3.50-3.80 (m, 4H), 3.00-3.20 (m, 2H), 2.90-3.00 (m, 2H), 2.75-2.85 (m, 2H), 2.60-2.70 (m, 1H), 2.20-2.50 (m, 2H), 1.90-2.00 (m, 1H), 1.80-1.90 (m, 1H), 1.70-1.80 (m, 1H), 1.60-1.70 (m, 1H), 1.50-1.60 (m, 1H), 1.00-1.50 (m, 9H). MS (APCI+) [M+H]+ 462.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 12 hours
  3. customThe reaction was quenched
  4. additionby pouring the reaction mixture into water (10 mL)
  5. extractionwas extracted with EtOAc (100 mL)
  6. washThe organic layer was washed with brine
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified with flash chromatography

出典と根拠

ORDレコード
ord-60ad8b2ff5574673a9e0703f5c30a166
出典データセット
uspto-grants-2012_12
特許番号
US08324221B2

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