Dimethylformamide → HCID 57337173, compound

HRID 2403651Notes

Reaction equation

HRID 2403651 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]([NH:10]/[N:11]=[C:12]1/[CH:13]=[CH:14][C:15]2([CH2:31][CH2:32]/1)[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])[CH2:17][CH2:16]2)([CH3:9])([CH3:8])[CH3:7].[CH3:33]N(C)C=O>>[C:6]([N:10]1[CH:33]=[C:32]2[C:12]([CH:13]=[CH:14][C:15]3([CH2:31]2)[CH2:16][CH2:17][N:18]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH2:19][CH2:20]3)=[N:11]1)([CH3:9])([CH3:7])[CH3:8]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 57336962HCID 57336962, compound

Product 1

HCID 57337173HCID 57337173, compoundYield 65%

Conditions

Temperature
0 °C

Procedure

(E)-benzyl 9-(2-tert-butylhydrazono)-3-azaspiro[5.5]undec-7-ene-3-carboxylate hydrochloride salt (8.00 g, 19.7 mmol) was dissolved in dichloromethane (100 mL) and treated with sodium bicarbonate (1.70 g, 19.7 mmol). The solution was stirred for 30 minutes and was then filtered and concentrated under reduced pressure to yield (E)-benzyl 9-(2-tert-butylhydrazono)-3-azaspiro[5.5]undec-7-ene-3-carboxylate. A 250 mL round bottom flask was charged with dimethylformamide (80 mL) and cooled to 0° C. Phosphorous oxychloride (5.51 mL, 59.1 mmol) was added dropwise over 2 minutes, and the solution was stirred for 30 minutes at 0° C. To this solution was added the (E)-benzyl 9-(2-tert-butylhydrazono)-3-azaspiro[5.5]undec-7-ene-3-carboxylate in dimethylformamide (15 mL) and the reaction was heated at 80° C. for 18 hours. The reaction was cooled to room temperature and concentrated under reduced pressure. The resultant oil was dissolved in ethyl acetate (500 mL) and washed with brine (2×150 mL). The aqueous layer was extracted with an additional 100 mL ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The resultant oil was purified by flash column chromatography (10-80% ethyl acetate/heptane) to yield 4.89 g (65%) of the title compound as a pale yellow oil. +ESI (M+H) 380.0; 1H NMR (400 MHz, CDCl3, δ): 7.25-7.36 (m, 5 H), 7.18 (s, 1 H), 6.57 (d, J=10.0 Hz, 1 H), 5.86 (d, J=10.0 Hz, 1 H), 5.12 (s, 2 H), 3.51-3.69 (m, 2 H), 3.36-3.53 (m, 2 H), 2.58 (s, 2 H), 1.59-1.74 (m, 2 H), 1.52-1.58 (m, 9 H), 1.41-1.53 (m, 2 H).

Workup

  1. temperaturethe reaction was heated at 80° C. for 18 hours
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe resultant oil was dissolved in ethyl acetate (500 mL)
  5. washwashed with brine (2×150 mL)
  6. extractionThe aqueous layer was extracted with an additional 100 mL ethyl acetate
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resultant oil was purified by flash column chromatography (10-80% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-444c988657ac454aba95ab68b9b357dd
Source dataset
uspto-grants-2014_08
Patent number
US08802688B2

Reaction notes

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