Sodium cyanoborohydride → 2-{2-[2-(1,3-Dioxo-1,3,dihydro-isoindol-2-yl)-2-(2-trimethylsilanyl-ethoxycarbonyl)-ethyl]-benzylamino}-4-methyl-valeric acid, tert-butyl ester

HRID 2714Notes

Reaction equation

HRID 2714 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[CH:12]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH:29]=O)[C:13]([O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])=[O:14].Cl.[C:32]([O:36][C:37](=[O:44])[C@H:38]([CH2:40][CH:41]([CH3:43])[CH3:42])[NH2:39])([CH3:35])([CH3:34])[CH3:33].C([BH3-])#N.[Na+]>CO.O1CCCC1>[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[CH:12]([C:13]([O:15][CH2:16][CH2:17][Si:18]([CH3:20])([CH3:19])[CH3:21])=[O:14])[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH2:29][NH:39][CH:38]([CH2:40][CH:41]([CH3:42])[CH3:43])[C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:44]

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydride2×HCID 12451443tert-butyl (2S)-2-amino-4-methylpentanoate hydrochlorideHCID 544841782-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-formyl-phenyl)-propionic acid, 2-trimethylsilanyl-ethyl ester

Product 1

HCID 1317205832-{2-[2-(1,3-Dioxo-1,3,dihydro-isoindol-2-yl)-2-(2-trimethylsilanyl-ethoxycarbonyl)-ethyl]-benzylamino}-4-methyl-valeric acid, tert-butyl esterYield 63%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-formyl-phenyl)-propionic acid, 2-trimethylsilanyl-ethyl ester (250 mg, 0.590 mmol) in methanol (15 mL) and treat with L-leucine tert-butyl ester hydrochloride (0.66 g, 3.0 mmol). Stir at room temperature for 2 hours with 3A molecular sieves, add sodium cyanoborohydride (0.6 mL of a 1.0M solution in tetrahydrofuran, 0.6 mmol), stir for 0.5 hours, add additional sodium cyanoborohydride (0.3 mL) and stir for 5 hours. Filter through filter aid, evaporate the solvent in vacuo and partition the residue between methylene chloride (100 mL) and saturated sodium hydrogen carbonate (40 mL). Dry (Na2SO4), evaporate the solvent in vacuo and purify by silica gel chromatography (5:1 hexane/ethyl acetate followed by 3:1 hexane/ethyl acetate) to give the title compound (221 mg, 63%).

Workup

  1. stirringstir for 5 hours
  2. filtrationFilter
  3. filtrationthrough filter aid
  4. customevaporate the solvent in vacuo
  5. custompartition the residue between methylene chloride (100 mL) and saturated sodium hydrogen carbonate (40 mL)
  6. dry with materialDry (Na2SO4)
  7. customevaporate the solvent in vacuo
  8. custompurify by silica gel chromatography (5:1 hexane/ethyl acetate followed by 3:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-47a0518a349f4b378e32db04cdc4b810
Source dataset
uspto-grants-1998_03
Patent number
US05731306

Reaction notes

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