Tetrahydrofuran → HCID 57691462, compound

HRID 1867636Notes

Reaction equation

HRID 1867636 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[CH2:6][O:7][CH2:8][C:9](N(OC)C)=[O:10].O1CCCC1.[O:29]1[CH2:34][CH2:33][CH2:32][O:31][CH:30]1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[Mg]Br>>[O:29]1[CH2:34][CH2:33][CH2:32][O:31][CH:30]1[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:40]=1[C:9](=[O:10])[CH2:8][O:7][CH2:6][C:5]1[CH:4]=[C:3]([C:2]([F:23])([F:22])[F:1])[CH:17]=[C:16]([C:18]([F:19])([F:21])[F:20])[CH:15]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 22960645HCID 22960645, compoundHCID 178419621HCID 178419621, compound

Product 1

HCID 57691462HCID 57691462, compound

Procedure

To a solution of 2-(3,5-bis(trifluoromethyl)benzyloxy)-N-methoxy-N-methylacetamide (5.0 g, 14 mmol) in tetrahydrofuran (20 mL, 247 mmol) at −78° C. was added (2-(1,3-dioxan-2-yl)phenyl)magnesium bromide (0.25M in tetrahydrofuran) (64 mL). The ice bath was replaced with a 0° C. bath and stirring continued for 1 h. The reaction was quenched by addition of saturated ammonium chloride. The mixture was diluted with pentane and the layers separated. The organics were washed with water, then brine, dried over magnesium sulfate, and concentrated. Flash chromatography (12% EtOAc/Hex) gave 3.20 g (49%) as a white crystalline solid. 1H-NMR (CDCl3, 300 MHz) δ 7.80 (s, 2H), 7.78 (s, 1H), 7.70 (d, J=7.6 Hz, 1H), 7.44 (m, 1H), 7.33 (m, 2H), 5.87 (s, 1H), 4.70 (s, 2H), 4.61 (s, 2H), 4.16 (dd, J=11.3, 4.9 Hz, 2H), 3.92 (m, 2H), 2.11 (m, 1H), 1.38 (d, J=13.7 Hz, 1H); 13C-NMR (CDCl3, 126 MHz) δ 202.2, 140.7, 136.9, 136.1, 131.7 (q, J=33.6 Hz), 130.9, 128.4, 127.7, 126.7, 123.4 (q, J=273 Hz), 121.7, 98.7, 75.2, 71.6, 67.4, 25.7.

Workup

  1. customwas replaced with a 0° C.
  2. customThe reaction was quenched by addition of saturated ammonium chloride
  3. additionThe mixture was diluted with pentane
  4. customthe layers separated
  5. washThe organics were washed with water
  6. dry with materialbrine, dried over magnesium sulfate
  7. concentrationconcentrated
  8. customFlash chromatography (12% EtOAc/Hex) gave 3.20 g (49%) as a white crystalline solid

Sources & evidence

ORD record
ord-46d84154005e47578d048de65084ab22
Source dataset
uspto-grants-2009_12
Patent number
US07632861B2

Reaction notes

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