Diethylene Glycol → HCID 58067258, compound

HRID 78984Notes

Reaction equation

[CH3:1][C:2]1([CH3:33])[CH2:8][C:7](=O)[CH2:6][CH2:5][C:4]([CH3:11])([CH3:10])[P:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[C:23]([CH:24]([CH3:26])[CH3:25])=[CH:22][C:21]([CH:27]([CH3:29])[CH3:28])=[CH:20][C:19]=1[CH:30]([CH3:32])[CH3:31].C(O)COCCO.O.NN.[OH-].[K+]>CCCCCCC.C(OCC)(=O)C>[CH3:33][C:2]1([CH3:1])[CH2:8][CH2:7][CH2:6][CH2:5][C:4]([CH3:10])([CH3:11])[P:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[C:19]([CH:30]([CH3:31])[CH3:32])=[CH:20][C:21]([CH:27]([CH3:29])[CH3:28])=[CH:22][C:23]=1[CH:24]([CH3:26])[CH3:25]

Participants

Conditions

Temperature: 210 °C

Procedure

A round bottom flask was charged with 2,2,7,7-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphepan-4-one (1.06 g, 2.29 mmol, 1.0 equiv) and purged with nitrogen for 15 minutes. Nitrogen-sparged diethylene glycol (12.0 mL, 126 mmol, 55 equiv) was added and the flask was equipped with a Claisen adapter and a Dean-Stark trap. The mixture was charged with hydrazine hydrate (1.01 mL, 11.4 mmol, 5 equiv, 55 wt % hydrazine) and potassium hydroxide (641 mg, 11.4 mmol, 5 equiv). The mixture was immersed in an oil bath at 175° C. under a nitrogen atmosphere. The temperature of the bath was gradually increased to 210° C. over 40 minutes and kept at that temperature for 7 hours. The reaction mixture was cooled to room temperature under a positive pressure of nitrogen and then the reaction mixture was diluted with heptane (20 mL) and ethyl acetate (20 mL). The phases were partitioned, and the organic layer was collected. The aqueous layer was washed with ethyl acetate (3×20 mL). The combined organic fractions were washed once with aqueous saturated sodium chloride (50 mL), dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. The crude product was purified by silica gel column chromatography (80-g column; gradient: 1.5 column volumes heptane, ramp up to 92:8 heptane:ethyl acetate over 8.5 column volumes, hold at 92:8 for 2 column volumes) to afford the title compound as a white solid (810 mg, >99 area % by HPLC, 79% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.00-7.83 (m, 1H), 7.33-7.26 (m, 2H), 7.22-7.13 (m, 1H), 6.97 (s, 2H), 2.91 (hept, J=6.9 Hz, 1H), 2.48 (hept, J=6.7 Hz, 2H), 1.77-1.60 (m, 6H), 1.60-1.47 (m, 2H), 1.29 (d, J=6.9 Hz, 6H), 1.21 (dd, J=8.2, 4.4 Hz, 12H), 0.96 (d, J=6.7 Hz, 6H), 0.82 (s, 3H), 0.78 (s, 3H). 13C NMR (100 MHz, CDCl3) δ ppm 148.0, 147.7, 147.2, 145.8, 137.0 (d, J=34 Hz), 136.7, 136.2 (d, J=2 Hz), 131.7 (d, J=7 Hz), 126.9, 125.1, 119.9, 46.3 (d, J=17 Hz), 35.1, 34.8, 34.3, 32.1, 31.9, 31.1 (d, J=3 Hz), 28.8 (d, J=3 Hz), 26.7, 26.2 (d, J=3 Hz), 24.4, 22.9 (d, J=2 Hz). 31P NMR (CDCl3, 202 MHz) δ ppm 20.1 (s). HRMS (TOF-ESI+) calcd for [M, C31H47P]+ 450.3415. Found 450.3429.

Workup

custompurged with nitrogen for 15 minutes
additionwas added
customthe flask was equipped with a Claisen adapter
customThe mixture was immersed in an oil bath at 175° C. under a nitrogen atmosphere
temperatureThe reaction mixture was cooled to room temperature under a positive pressure of nitrogen
customThe phases were partitioned
customthe organic layer was collected
washThe aqueous layer was washed with ethyl acetate (3×20 mL)
washThe combined organic fractions were washed once with aqueous saturated sodium chloride (50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated on a rotary evaporator
customThe crude product was purified by silica gel column chromatography (80-g column

Sources & evidence

ORD record: ord-5a2e22d877094585b7d003fe28a476aa
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841487B2

Reaction notes

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