1,4-Dioxane → HCID 68777387, compound

HRID 730529Notes

Reaction equation

HRID 730529 reaction equation
[CH2:1]([O:4][C:5]([C:7]1[N:8]([NH:13][CH2:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:10]([F:12])[CH:11]=1)=[O:6])[CH:2]=[CH2:3].C[CH:20](C(Cl)=O)[C:21](Cl)=[O:22].[C:27](=[O:30])(O)[O-:28].[Na+].O1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>>[CH2:1]([O:4][C:5]([C:7]1[N:8]([N:13]([C:21](=[O:22])[CH2:20][C:27]([O:28][CH3:33])=[O:30])[CH2:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:10]([F:12])[CH:11]=1)=[O:6])[CH:2]=[CH2:3].[CH2:1]([O:4][C:5]([C:7]1[N:8]([N:13]([C:21](=[O:22])[CH2:37][C:36]([O:35][CH2:34][CH3:33])=[O:28])[CH2:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:10]([F:12])[CH:11]=1)=[O:6])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 10931669MethylmalonylchlorideHCID 59853584HCID 59853584, compound

Product 2

HCID 59853571HCID 59853571, compoundHCID 68777387HCID 68777387, compoundYield 100%

Conditions

Temperature
100 °C

Procedure

4-Fluoro-1-(3-methyl-butylamino)-1H-pyrrole-2-carboxylic acid allyl ester (Example 14g, 0.24 g, 0.944 mmol) was dissolved in anhydrous 1,4-dioxane (10 mL) and methyl malonyl chloride was added under a nitrogen atmosphere. The reaction mixture was heated to 100° C. for 1 h. Upon cooling to 25° C., saturated aqueous sodium bicarbonate solution was added and the product was extracted with 50% ethyl acetate/hexanes. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford the crude desired product, 1-[(2-ethoxycarbonyl-acetyl)-(3-methyl-butyl)-amino]-4-fluoro-1H-pyrrole-2-carboxylic acid allyl ester (0.335 g, 0.944 mmol, 100% yield) as a pale yellow oil, which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ: 0.90 (3H, d, J=4.6 Hz), 0.92 (3H, d, J=5.2 Hz), 1.37-1.46 (1H, m), 1.54-1.64 (1H, m), 1.69-1.78 (1H, m), 3.13 (2H, d, J=3.1 Hz), 3.70 (3H, s), 4.16-4.26 (2H, m), 4.73 (2H, d, J=5.5 Hz), 5.28-5.31 (1H, m), 5.37 (1H, dd, J1=17.2 Hz, J2=1.6 Hz), 5.91-6.01 (1H, m), 6.69-6.76 (2H, m).

Workup

  1. temperatureUpon cooling to 25° C.
  2. extractionthe product was extracted with 50% ethyl acetate/hexanes
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a17da366e4484bf6afe9d6d3e49579e6
Source dataset
uspto-grants-2009_09
Patent number
US07582754B2

Reaction notes

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