Bromoacetonitrile → (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate

HRID 451996노트

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HRID 451996 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([OH:23])[C@@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[H-].[Na+].Br[CH2:27][C:28]#[N:29]>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([O:23][CH2:27][C:28]#[N:29])[C@@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:11]2)[CH:5]=[C:6]([F:8])[CH:7]=1

참가 물질

5

반응물 3

HCID 11534Bromoacetonitrile2회HCID 24758Sodium hydride2회HCID 58017388(R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate

생성물 1

HCID 67365681(R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate수율 100%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
-20 °C

실험 절차

To a solution of (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (3.5 g, 10.2 mmol) in CH3CN (140 mL), NaH (1.2 g, 30.6 mmol) was added at 0° C. The mixture was stirred for 1 hr. Then the mixture was cooled to −20° C., bromoacetonitrile (3.6 g, 30.6 mmol) was added dropwise. The mixture was allowed warm to 0° C. gradually. Another batch of NaH and bromoacetonitrile was added in the same manner. The mixture was quenched with H2O and extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrate to give the crude (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate (4.4, 100%).

후처리

  1. temperatureThe mixture was allowed warm to 0° C. gradually
  2. customThe mixture was quenched with H2O
  3. extractionextracted with CH2Cl2
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrate

출처 및 근거

ORD 기록
ord-273337744f504b7da96f3ee13b0e0aa9
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08487108B2

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