4-Bromobutyronitrile → (R)-tert-butyl 3-((R)-(3-chlorophenyl)(3-cyanopropoxy)methyl)piperidine-1-carboxylate

HRID 451908

반응식

HRID 451908 반응식
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C@H:10]([OH:24])[C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)[CH:7]=[CH:8][CH:9]=1.Br[CH2:26][CH2:27][CH2:28][C:29]#[N:30].[NH4+].[Cl-]>CC#N.C(OCC)(=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([C@H:10]([O:24][CH2:26][CH2:27][CH2:28][C:29]#[N:30])[C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:12]2)[CH:7]=[CH:8][CH:9]=1

참가 물질

7

반응물 4

HCID 214124-BromobutyronitrileHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 445550221-Piperidinecarboxylic acid, 3-[(R)-(3-chlorophenyl)hydroxymethyl]-, 1,1-dimethylethyl ester, (3R)-

생성물 1

HCID 68714485(R)-tert-butyl 3-((R)-(3-chlorophenyl)(3-cyanopropoxy)methyl)piperidine-1-carboxylate수율 23.5%

시약·촉매·용매 2

HCID 6342Acetonitrile용매2회HCID 8857Ethyl Acetate용매

실험 절차

To a suspension of NaH (763 mg, 19.1 mmol) and (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (1.55 g, 4.77 mmol) in CH3CN (20 mL) at 0-5° C. was added dropwise a solution of 4-bromobutyronitrile (3.17 g, 21.5 mmol) in CH3CN (5 mL), the reaction mixture was stirred for overnight at rt. The reaction mixture was poured into saturated aqueous NH4Cl, ethyl acetate (50 mL) was added. The organic layer was washed with water (3×20 mL) and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative HPLC to afford (R)-tert-butyl 3-((R)-(3-chlorophenyl)(3-cyanopropoxy)methyl)piperidine-1-carboxylate (0.44 g, 21% yield). 1H NMR (CD3OD, 400 MHz) δ 7.38-7.28 (m, 3H), 7.22 (m, 1H), 4.22 (m, 1H), 4.02 (d, 1H), 3.86 (d, 1H), 3.34 (m, 2H), 2.77 (q, 2H), 2.56 (t, 2H), 1.62 (m, 1H), 1.59 (m, 1H), 1.43 (s, 9H), 1.35-1.25 (m, 3H), 1.12 (d, 1H).

후처리

  1. additionwas added
  2. washThe organic layer was washed with water (3×20 mL) and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-695bdd89cf9542e49e108f5ae34bf9c9
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08487108B2

연결된 노트

불러오는 중…