2-Hydroxyisobutyric acid → HCID 89668696, compound

HRID 1482284Notes

Reaction equation

HRID 1482284 reaction equation
C(Cl)(=O)C(Cl)=O.[CH:7]1[C:19]2[CH:18]([CH2:20][O:21][C:22]([N:24]3[CH2:28][CH2:27][CH2:26][C@H:25]3[C:29]([OH:31])=[O:30])=[O:23])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]=2[CH:10]=[CH:9][CH:8]=1.C(N(C(C)C)C(C)C)C.O[C:42]([CH3:47])([CH3:46])[C:43]([OH:45])=[O:44]>C(Cl)Cl.CN(C)C=O>[CH:16]1[C:17]2[CH:18]([CH2:20][O:21][C:22]([N:24]3[CH2:28][CH2:27][CH2:26][C@H:25]3[C:29]([O:31][C:42]([CH3:47])([CH3:46])[C:43]([OH:45])=[O:44])=[O:30])=[O:23])[C:19]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12]=2[CH:13]=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 116712-Hydroxyisobutyric acidHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 688135Fmoc-Pro-OH

Product 1

HCID 89668696HCID 89668696, compoundYield 98.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (1.17 mL, 13.3 mmol) was added dropwise to a solution of (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)pyrrolidine-2-carboxylic acid (Fmoc-Pro-OH) (3.00 g, 8.89 mmol) and N,N-dimethylformamide (34 μL, 0.445 mmol) in methylene chloride (36 mL) with stirring at 0° C. under a nitrogen atmosphere, and the reaction mixture was then stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, the resulting residue was mixed with methylene chloride (36 mL), N-ethyldiisopropylamine (DIPEA) (4.66 mL, 26.7 mmol) and 2-hydroxy-2-methylpropanoic acid (2.78 g, 26.7 mmol) at 0° C., and the reaction mixture was stirred at room temperature for 2 hours. The reaction solution was washed with 1 N hydrochloric acid twice and a saturated aqueous sodium chloride solution twice, dried over sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution) to afford (S)-2-((1-(((9H-fluoren-9-yl)methoxy)carbonyl)pyrrolidine-2-carbonyl)oxy)-2-methylpropanoic acid (Fmoc-Pro-HOGly(Me)2-OH) (Compound SP636) (3.70 g, 8.74 mmol, 98%).

Workup

  1. stirringthe reaction mixture was then stirred at room temperature for 1 hour
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. stirringthe reaction mixture was stirred at room temperature for 2 hours
  4. washThe reaction solution was washed with 1 N hydrochloric acid twice
  5. dry with materiala saturated aqueous sodium chloride solution twice, dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution)

Sources & evidence

ORD record
ord-533a64984f3049b2935321275ae6967f
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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