Acetic Acid → tert-butyl(2S,3S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3-methylpentanoate

HRID 643075Notes

Reaction equation

HRID 643075 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH:13]=O.Cl.[C:16]([O:20][C:21](=[O:28])[C@H:22]([C@H:24]([CH2:26][CH3:27])[CH3:25])[NH2:23])([CH3:19])([CH3:18])[CH3:17].C([BH3-])#N.[Na+].C(O)(=O)C>CO>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][NH:23][C@@H:22]([C@@H:24]([CH3:25])[CH2:26][CH3:27])[C:21]([O:20][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:28]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 76201Phthalylglycine aldehydeHCID 5003444Sodium cyanoborohydrideHCID 11687228tert-Butyl isoleucinate--hydrogen chloride (1/1)

Product 1

HCID 66891692tert-butyl(2S,3S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3-methylpentanoateYield 61.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of Example 28A (12.1 g) in methanol (20 mL) was added L-isoleucine tert-butyl ester hydrochloride (13.0 g, 58 mmol), sodium cyanoborohydride (7.3 g, 116 mmol), and acetic acid (2 mL). The resulting solution was stirred for 3 hrs at 25° C. and the methanol removed under vacuum, dichloromethane (500 mL) added, and the solution washed with aqueous NaHCO3 (2×300 mL). The organic layer was concentrated to give 12.9 g of the title compound.

Workup

  1. customthe methanol removed under vacuum, dichloromethane (500 mL)
  2. additionadded
  3. washthe solution washed with aqueous NaHCO3 (2×300 mL)
  4. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-bf56f61c5ea0441fb46ffe980ac18e12
Source dataset
uspto-grants-2010_04
Patent number
US07696226B2

Reaction notes

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