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

HRID 415953ノート

反応式

HRID 415953 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-e671def63261458497e782b3636af171
出典データセット
uspto-grants-2012_01
特許番号
US08088771B2

反応ノート

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