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

HRID 1839554노트

반응식

HRID 1839554 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-18b9955c36b04114982ad16af4260a14
출처 데이터셋
uspto-grants-2004_01
특허 번호
US06677364B2

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