Cyanocyclobutane → 1-(4-Bromopyridin-2-yl)cyclobutane-1-carbonitrile

HRID 444871

反応式

HRID 444871 の反応式
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14](F)[CH:13]=1.[CH:19]1([C:23]#[N:24])[CH2:22][CH2:21][CH2:20]1>C1(C)C=CC=CC=1>[Br:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14]([C:19]2([C:23]#[N:24])[CH2:22][CH2:21][CH2:20]2)[CH:13]=1

参加物

5

反応物 3

HCID 78148CyanocyclobutaneHCID 2733832Lithium HexamethyldisilazideHCID 27628514-Bromo-2-fluoropyridine

生成物 1

HCID 574170941-(4-Bromopyridin-2-yl)cyclobutane-1-carbonitrile収率 69%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

LiHMDS (1M in toluene, 17.7 mL, 17.7 mmol, 3.1 eq) is added dropwise to a cold (−5° C.) solution of 4-bromo-2-fluoro-pyridine [Marsais, F. et al, Journal of Organic Chemistry, (1992), 57, 565-573] (1 g, 5.7 mmol) and cyclobutanecarbonitrile (1.39 g, 17.1 mmol, 3 eq) in toluene (20 mL). The reaction mixture is allowed to warm to rt, stirred for 5 h, quenched by addition of a saturated solution of NaHCO3 (50 mL) and filtered through a pad of celite. The filtrate is extracted with EtOAc (3×75 mL). The organic phase is washed with a saturated solution of NaHCO3 (2×50 mL), dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel column chromatography (Hex/EtOAc, 1:0→95:5) to afford 933 mg of the title compound as a yellow oil: ESI-MS: 237.0/239.0 [M+H]+; tR=4.27 min (System 1); TLC: Rf=0.30 (Hex/EtOAc, 9:1).

後処理

  1. customquenched by addition of a saturated solution of NaHCO3 (50 mL)
  2. filtrationfiltered through a pad of celite
  3. extractionThe filtrate is extracted with EtOAc (3×75 mL)
  4. washThe organic phase is washed with a saturated solution of NaHCO3 (2×50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel column chromatography (Hex/EtOAc, 1:0→95:5)

出典と根拠

ORDレコード
ord-283b4db5ba7240d08b33a53c02e7bbff
出典データセット
uspto-grants-2013_07
特許番号
US08476268B2

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