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

HRID 529137

반응식

HRID 529137 반응식
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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0e77ad09d8124979836049052beeae2e
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346805B2

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