Bis(2-bromoethyl) ether → 4-(4-Cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester

HRID 218052노트

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HRID 218052 반응식
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]#[N:12])=[CH:6][C:5]=1C.Br[CH2:16][CH2:17][O:18][CH2:19][CH2:20]Br.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:5]=[CH:6][C:7]([C:10]2([C:11]#[N:12])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[CH:8][CH:9]=1

참가 물질

5

반응물 3

HCID 21521Bis(2-bromoethyl) etherHCID 3251421Potassium bis(trimethylsilyl)amideHCID 66619307Methyl 4-(cyanomethyl)-2-methylbenzoate

생성물 1

HCID 666188074-(4-Cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

Methyl 4-(cyanomethyl)-benzoic acid methyl ester (1.92 g, 11.01 mmol) and 1-bromo-2-(2-bromo-ethoxy)-ethane (12.56 mL, 55.04 mmol) were combined in THF (15 mL) and cooled down to 0° C. Potassium bis(trimethylsilyl)-amide (0.5M in toluene, 48.3 mL, 24.21 mmol, 2.2 eq) was added over a period of 15 minutes and then warmed up to room temperature and stirred for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried with MgSO4 and evaporated under vacuum. The crude product was purified by chromatography on silica gel (25% EtOAc/hexanes) to afford 4-(4-cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester. To a solution of 4-(4-cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester (1.55 g 6.32 mmol) in MeOH (10 mL) was added Et3N (3 mL). H2S was bubbled into the solution. The reaction vessel was stirred at room temperature for 3 days. The reaction mixture was then evaporated and purified by silica gel chromatography (33% EtOAc/hexanes) to afford 4-(4-thiocarbamoyl-tetrahydro-pyran-4-yl)-benzoic acid methyl ester.

후처리

  1. temperaturewarmed up to room temperature
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried with MgSO4
  4. customevaporated under vacuum
  5. customThe crude product was purified by chromatography on silica gel (25% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-e95aa6f3de114c7e963d319172a1e12f
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08198299B2

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