Acetic Acid → HCID 86619835, compound

HRID 1994295Notes

Reaction equation

HRID 1994295 reaction equation
[C:1]([O:5][C:6](=[O:12])[C@@H:7]([CH:9]([CH3:11])[CH3:10])[NH2:8])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.[O:17]=[C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20](=[O:27])[N:19]1[CH2:28][CH:29]=O.C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>CO.C1COCC1>[O:17]=[C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20](=[O:27])[N:19]1[CH2:28][CH2:29][NH:8][C@H:7]([CH:9]([CH3:10])[CH3:11])[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:12]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 76201Phthalylglycine aldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 6931638tert-butyl D-valinate

Product 1

HCID 86619835HCID 86619835, compoundYield 67.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(R)-Valine t-butyl ester (4.9 g; 28.28 mmol) was dissolved in methanol (100 ml). Acetic acid (1.62 ml; 28.28 mmol) and (1,3-dioxo-1,3-dihydroisoindol-2-yl)-acetaldehyde (5.40 g; 28.28 mmol) were added thereto. Then, sodium cyanoborohydride (1.95 g; 31.11 mmol) dissolved in THF (20 ml) was added. The mixture was stirred at RT for 6 h and then saturated NaHCO3 solution (200 ml) was added. Methanol was removed under reduced pressure, and the residue was extracted with EtOAc (3×; 100 ml). The combined organic phases were dried over MgSO4. Removal of the solvent under reduced pressure and purification of the residue by column chromatography (SiO′) resulted in t-butyl (R)-2-(2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethylamino)-3-methylbutyrate (6.60 g; 19.05 mmol). MS: 347.20 (M+H); Rt: 1.02 min (method: gradient 0 min 96% H2O (0.05% TFA) 2.0 min 95% acetonitrile, 95% acetonitrile to 2.4 min, 4% acetonitrile 2.45 min; flow rate 1 ml/min; column 0.4 μL (YMC J'sphere ODS H80 20X2 1.4μ); 30° C.)

Workup

  1. additionwas added
  2. customMethanol was removed under reduced pressure
  3. extractionthe residue was extracted with EtOAc (3×; 100 ml)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. customRemoval of the solvent
  6. customunder reduced pressure and purification of the residue by column chromatography (SiO′)

Sources & evidence

ORD record
ord-4d3fd17509e545e4a5e8e80310215768
Source dataset
uspto-grants-2010_01
Patent number
US07652143B2

Reaction notes

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