Ethyl bromoacetate → ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate

HRID 1839554ノート

反応式

HRID 1839554 の反応式
Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[F:8][C:9]1[CH:10]=[C:11]([OH:23])[CH:12]=[C:13]([C:15]2([O:21][CH3:22])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:14]=1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[F:8][C:9]1[CH:10]=[C:11]([CH:12]=[C:13]([C:15]2([O:21][CH3:22])[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)[CH:14]=1)[O:23][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4]

参加物

5

反応物 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 117362763-Fluoro-5-(4-methoxytetrahydro-2H-pyran-4-yl)phenol

生成物 1

HCID 22246123ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate収率 73.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of ethyl bromoacetate (0.5 g, 3 mmol), 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenol (Example 8, Step 4) (0.3 g, 1.3 mmol) and K2CO3 (0.11 g, 0.8 mmol) in dimethylformamide (5.0 mL) was stirred at room temperature for 16 h under an argon atmosphere. The reaction mixture was partitioned between 5% citric acid (25 mL) and EtOAc (25 mL). The organic phase was washed with water, dried (Na2SO4), filtered and concentrated. The resulting syrup was purified by flash column chromatography on silica gel, eluting with 25% EtOAc in hexane, to give 0.3 g (73%) of ethyl 3-fluoro-5(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate as a colorless viscous liquid: 1H NMR (CDCl3/300 MHz) δ 6.77 (d,2H, J=10.5 Hz), 6.52 (d, 1H, J=10.5 Hz), 4.61 (s, 2H), 4.28 (q, 2H, J=6.9 Hz), 3.82 (m, 4H), 2.99 (s, 3H), 1.92 (m, 4H), 1.31 (t, 3H, J=6.9 Hz). FABMS m/z=313 (M+H). HRMS calcd for C16H22FO5313.1451, found 313.1399.

後処理

  1. customThe reaction mixture was partitioned between 5% citric acid (25 mL) and EtOAc (25 mL)
  2. washThe organic phase was washed with water
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting syrup was purified by flash column chromatography on silica gel
  7. washeluting with 25% EtOAc in hexane

出典と根拠

ORDレコード
ord-18b9955c36b04114982ad16af4260a14
出典データセット
uspto-grants-2004_01
特許番号
US06677364B2

反応ノート

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