Sodium Bicarbonate → Methyl 3-{2-[(acetyloxy)methyl]-4-[(tert-butoxycarbonyl)amino]-3-methylphenyl}-2-{[(benzyloxy)carbonyl]amino}prop-2-enoate

HRID 132155Notes

Reaction equation

HRID 132155 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]([CH3:21])=[C:11]([C:17](I)=[CH:18][CH:19]=1)[CH2:12][O:13][C:14](=[O:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22][O:23][C:24]([C:26]([NH:28][C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30])=[CH2:27])=[O:25].C(=O)(O)[O-].[Na+]>O.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:22][O:23][C:24](=[O:25])[C:26]([NH:28][C:29]([O:31][CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)=[O:30])=[CH:27][C:17]1[CH:18]=[CH:19][C:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[C:10]([CH3:21])[C:11]=1[CH2:12][O:13][C:14](=[O:16])[CH3:15]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 3525700Z-Dehydro-Ala-OMeHCID 534147073-(Tert-butoxycarbonylamino)-6-iodo-2-methylbenzyl acetate

Product 1

HCID 53415138Methyl 3-{2-[(acetyloxy)methyl]-4-[(tert-butoxycarbonyl)amino]-3-methylphenyl}-2-{[(benzyloxy)carbonyl]amino}prop-2-enoateYield 69%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 16212273Tetrabutylammonium chloride hydrateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Palladium (II) acetate (105 mg, 0.43 mmol) was added to a mixture of acetic acid 3-tert-butoxycarbonylamino-6-iodo-2-methyl-benzyl ester (2.89 g, 7.1 mmol), Z-dehydroalanine methyl ester (2.20 g, 9.4 mmol), tetrabutylammonium chloride hydrate (2.70 g, 9.7 mmol), and sodium bicarbonate (1.80 g, 21.4 mmol) in THF (100 mL). Reaction was heated at reflux for 3.75 hours. Mixture was cooled to room temperature then filtered through a plug of silica gel eluting 70% ethyl acetate-hexanes (500 mL). Filtrate was concentrated in vacuo. Silica gel chromatography afforded the title compound as a yellow solid in 69% yield. 1H NMR (300 MHz, CDCl3): δ=7.79 (d, J=8.4, 1H), 7.42 (s, 1H), 7.27 (m, 6H), 6.30 (s, 1H), 5.11 (s, 2H), 5.02 (s, 2H), 3.81 (s, 3H), 2.21 (s, 3H), 2.02 (s, 3H), 1.51 (s, 9H). MS m/e (M−H)−=511.0.

Workup

  1. customReaction
  2. temperaturewas heated
  3. temperatureat reflux for 3.75 hours
  4. filtrationthen filtered through a plug of silica gel eluting 70% ethyl acetate-hexanes (500 mL)
  5. concentrationFiltrate was concentrated in vacuo

Sources & evidence

ORD record
ord-b38fd3b1cfa5435a8eba00334cb307ce
Source dataset
uspto-grants-2008_06
Patent number
US07384930B2

Reaction notes

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