(4-Nitrophenyl)acetic acid → HCID 22397952, compound

HRID 1071277Notes

Reaction equation

HRID 1071277 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([OH:13])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].O.OC1C2N=NNC=2C=CC=1.Cl.C([O:28][C:29](=[O:49])[CH:30]([NH:42][C:43]([O:45][CH2:46][CH:47]=[CH2:48])=[O:44])[CH2:31][C:32]1[O:36][N:35]=[C:34]([CH:37]2[CH2:41][CH2:40][CH2:39][NH:38]2)[CH:33]=1)C.C(N(CC)CC)C>CN(C)C=O.O>[CH2:46]([O:45][C:43]([NH:42][CH:30]([CH2:31][C:32]1[O:36][N:35]=[C:34]([CH:37]2[CH2:41][CH2:40][CH2:39][N:38]2[C:11](=[O:13])[CH2:10][C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=2)[CH:33]=1)[C:29]([OH:49])=[O:28])=[O:44])[CH:47]=[CH2:48]

Participants

7

Reactant 4

HCID 4661(4-Nitrophenyl)acetic acidHCID 8471TriethylamineHCID 69735596HCID 69735596, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 22397952HCID 22397952, compoundYield 17.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A dimethyl formamide (82 mL) solution of 4-nitrophenylacetic acid (1.61 g, 8.87 mmol) in dimethyl formamide (82 mL) was stirred with 4-hydroxybenzotriazole monohydrate (1.40 g, 10.4 mmol) for 10 minutes. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimde hydrochloride (1.86 g, 9.72 mmol) was added and the mixture was stirred until all 1-(3-dimethylaminopropyl)-3-ethylcarbodiimde hydrochloride had dissolved. To this solution, 2-allyloxycarbonylamino-3-(3-pyrrolidin-2-yl-isoxazol-5-yl)-propionic acid ethyl ester hydrochloride from Example 1C (3.16 g, 8.25 mmol) was added and the mixture stirred 30 minutes followed by addition of triethyl amine (1.26 mL, 9.04 mmol). After the reaction had stirred at room temperature over night it was poured into water and extracted with ethyl acetate three times. The combined extracts were washed with a saturated solution of sodium bicarbonate, water (2×) and brine. The organic portion was dried over magnesium sulfate and concentrated. The resulting residue was chromatographed on a Biotage Flash 40S column eluting with ethyl acetate/hexanes (5:1) to yield the title compound as a yellow oil (674 mg, 15%). MS (Cl) m/z 501.3 (M+1). Additionally, starting material 2-allyloxycarbonylamino-3-(3-pyrrolidin-2-yl-isoxazol-5-yl)-propionic acid ethyl ester was recovered (2.15 g, 75%). MS (Cl) m/z 338.1 (M+1)

Workup

  1. dissolutionhad dissolved
  2. stirringAfter the reaction had stirred at room temperature over night it
  3. extractionextracted with ethyl acetate three times
  4. washThe combined extracts were washed with a saturated solution of sodium bicarbonate, water (2×) and brine
  5. dry with materialThe organic portion was dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was chromatographed on a Biotage Flash 40S column
  8. washeluting with ethyl acetate/hexanes (5:1)

Sources & evidence

ORD record
ord-f9f5bd991a3b407486bb4da3810b45c9
Source dataset
uspto-grants-2005_06
Patent number
US06903128B2

Reaction notes

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