Diethylene Glycol → 1-(2-(2,2,6,6-Tetramethylphosphinan-1-yl)phenyl)-1H-pyrrole

HRID 874031Notes

Reaction equation

HRID 874031 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[P:12]2[C:17]([CH3:19])([CH3:18])[CH2:16][C:15](=O)[CH2:14][C:13]2([CH3:22])[CH3:21])[CH:5]=[CH:4][CH:3]=[CH:2]1.C(O)COCCO.O.NN.[OH-].[K+]>O.C(OCC)(=O)C>[CH3:21][C:13]1([CH3:22])[CH2:14][CH2:15][CH2:16][C:17]([CH3:18])([CH3:19])[P:12]1[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[N:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 8117Diethylene GlycolHCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 58067311HCID 58067311, compound

Product 1

HCID 666785411-(2-(2,2,6,6-Tetramethylphosphinan-1-yl)phenyl)-1H-pyrroleYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
210 °C

Procedure

A round bottom flask was charged with 1-(2-(1H-pyrrol-1-yl)phenyl)-2,2,6,6-tetramethylphosphinan-4-one (878 mg, 2.80 mmol, 1.0 equiv) and purged with nitrogen for 15 minutes. Then nitrogen-sparged diethylene glycol (14.7 mL, 154 mmol, 55 equiv) was added and the flask was equipped with a Claisen adapter and a Dean-Stark trap. The flask was further charged with hydrazine hydrate (1.24 mL, 14.0 mmol, 5 equiv, 55 wt % hydrazine) and potassium hydroxide (786 mg, 14.0 mmol, 5 equiv), and the mixture was immersed in an oil bath at 60° C. The temperature of the bath was gradually increased to 210° C. over 1 hour and kept at that temperature for 7 hours. The reaction mixture was cooled to room temperature under a positive pressure of nitrogen and then diluted with water (50 mL) and ethyl acetate (20 mL). The phases were partitioned, and the organic layer was collected. The aqueous layer was washed with ethyl acetate (4×20 mL), and the combined organic fractions were washed once with aqueous saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated on a rotary evaporator to afford the title compound as a pale yellow solid (811 mg, 91 area % by HPLC, 97% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.96-7.83 (m, 1H), 7.35-7.22 (m, 2H), 7.22-7.17 (m, 1H), 6.72-6.66 (m, 2H), 6.20 (t, J=2.1 Hz, 2H), 1.87-1.71 (m, 2H), 1.71-1.56 (m, 2H), 1.50-1.33 (m, 2H), 1.11 (s, 3H), 1.06 (s, 3H), 0.76 (d, J=9.7 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ ppm 149.4-146.8 (m), 134.7 (d, J=4 Hz), 129.0, 127.8 (d, J=3 Hz), 126.5, 123.3 (d, J=3 Hz), 107.9, 37.6, 31.4, 31.1, 30.2 (d, J=7 Hz), 29.6 (d, J=18 Hz), 20.5. 31P NMR (CDCl3, 202 MHz) δ ppm −7.6 (s).

Workup

  1. custompurged with nitrogen for 15 minutes
  2. additionwas added
  3. customthe flask was equipped with a Claisen adapter
  4. customthe mixture was immersed in an oil bath at 60° C
  5. temperatureThe reaction mixture was cooled to room temperature under a positive pressure of nitrogen
  6. customThe phases were partitioned
  7. customthe organic layer was collected
  8. washThe aqueous layer was washed with ethyl acetate (4×20 mL)
  9. washthe combined organic fractions were washed once with aqueous saturated sodium chloride
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-3dd4f55a81aa4c4d81fbbbb89aa589d8
Source dataset
uspto-grants-2015_03
Patent number
US08975443B2

Reaction notes

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