Ethyl Acetate → HCID 57692600, compound

HRID 1511564Notes

Reaction equation

HRID 1511564 reaction equation
C[C@@:2]1([C:27]([O-:29])=[O:28])[CH2:6][C@@H:5]([O:7][C:8]([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3Br)[CH2:11]2)=[O:9])[CH2:4][N:3]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].[CH3:30][C:31]([CH3:46])([CH3:45])[C@@H:32]([C:42]([OH:44])=[O:43])[NH:33][C:34]([O:36][CH2:37][CH2:38][CH2:39][C:40]#[CH:41])=[O:35].[C:47]([O-])(O)=O.[Na+].CCOC(C)=O>C1COCC1.N1CCCC1.[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:23]([O:22][C:20]([N:3]1[C@H:2]([C:27]([O:29][CH3:47])=[O:28])[CH2:6][C@@H:5]([O:7][C:8]([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[C:41]#[C:40][CH2:39][CH2:38][CH2:37][O:36][C:34]([NH:33][C@H:32]([C:42]([OH:44])=[O:43])[C:31]([CH3:46])([CH3:45])[CH3:30])=[O:35])[CH2:11]2)=[O:9])[CH2:4]1)=[O:21])([CH3:25])([CH3:24])[CH3:26]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 574311933-Methyl-N-{[(pent-4-yn-1-yl)oxy]carbonyl}-L-valineHCID 86610193HCID 86610193, compound

Product 1

HCID 57692600HCID 57692600, compoundYield 99%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 31268PyrrolidineSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 1-tert-butyl 2-methyl-(2S,4R)-4-{[(4-bromo-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate (100 mg, 0.21 mmol) and 3-methyl-N-[(pent-4-yn-1-yloxy)carbonyl]-L-valine (103 mg, 0.43 mmol) in THF (1 mL) and pyrrolidine (1 mL) was purged with nitrogen. Copper iodide (4 mg, 0.02 mmol) and Pd(PPh3)4 (25 mg, 0.02 mmol) were added and the reaction mixture was heated for 30 min at 70° C. under nitrogen. The resulting mixture was poured into saturated aqueous NaHCO3 and EtOAc, the organic layer separated and washed twice with 10% citric acid solution, then brine and dried over Na2SO4. The residue was purified by column chromatography on silica gel (eluting with 90:10:1 DCM:MeOH:NH4OH) and concentrated to give N-[({5-[2-({[(3R,5S)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)pyrrolidin-3-yl]oxy}carbonyl)-2,3-dihydro-1H-isoindol-4-yl]pent-4-yn-1-yl}oxy)carbonyl]-3-methyl-L-valine (131 mg, 99% yield) as colorless oil. LRMS (ESI) m/z 530.5 [(M+H)+; calcd for C27H36N3O8: 530.6].

Workup

  1. customthe organic layer separated
  2. washwashed twice with 10% citric acid solution
  3. dry with materialbrine and dried over Na2SO4
  4. customThe residue was purified by column chromatography on silica gel (eluting with 90:10:1 DCM:MeOH:NH4OH)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-64109b2799bf4528ae69d5c8ec813278
Source dataset
uspto-grants-2012_07
Patent number
US08216999B2

Reaction notes

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