Water → Tert-butyl 4-((2-(cyanomethyl)-6-methoxyphenoxy)methyl)piperidine-1-carboxylate

HRID 253236

反応式

HRID 253236 の反応式
[OH:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:10][C:11]#[N:12].CS(O[CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C.[Cl-].[Na+].O.C(OCC)(=O)C>[C:11]([CH2:10][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([O:8][CH3:9])[C:2]=1[O:1][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[CH2:21][CH2:20]1)#[N:12]

参加物

8

反応物 4

HCID 962WaterHCID 10796Cesium carbonateHCID 1426432-Hydroxy-3-methoxyphenylacetonitrileHCID 2765838Tert-butyl 4-(methylsulfonyloxymethyl)piperidine-1-carboxylate

生成物 1

HCID 66890287Tert-butyl 4-((2-(cyanomethyl)-6-methoxyphenoxy)methyl)piperidine-1-carboxylate収率 81%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
70 °C

実験手順

To a solution of 2-hydroxy-3-methoxyphenylacetonitrile (1 g, 6.1 mmol) in DMF (12 mL) was added 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (1.8 g, 6.1 mmol) and cesium carbonate (4.0 g, 12.2 mmol). The mixture was heated to 70° C. for 3 h and then cooled to rt. Water and ethyl acetate were added followed by brine to reduce emulsification. The layers were partitioned, and the aqueous phase was extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate) to provide 1.77 g of 1,1-dimethylethyl 4-({[2-(cyanomethyl)-6-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (4.9 mmol, 81% yield) as a yellow syrup. 1H NMR (400 MHz, CDCl3): δ7.03 (t, 1H), 6.93 (dd, 1H), 6.88 (dd, 1H), 4.14 (br m, 2H), 3.88 (br d, 2H), 3.84 (s, 3H), 3.70 (s, 2H), 2.00 (m, 1H), 1.86 (br d, 2H), 1.47 (s, 9H), 1.35-1.25 (m, 2H).

後処理

  1. temperaturecooled to rt
  2. customThe layers were partitioned
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate)

出典と根拠

ORDレコード
ord-13b83ae05be84708ac1b04dd2c0f93b5
出典データセット
uspto-grants-2011_01
特許番号
US07872014B2

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