Dimethyl itaconate → Methyl (+)-3-carbomethoxy-4-[2-bis(tert-butoxycarbonyl)aminomethyl-4-methoxyphenyl]-3-butenoate

HRID 2416681Notes

Reaction equation

HRID 2416681 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:16][C:17]1[CH:18]=[C:19]([O:24][CH3:25])[CH:20]=[CH:21][C:22]=1Br)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:26]([O:35][CH3:36])(=[O:34])[C:27]([CH2:29][C:30]([O:32][CH3:33])=[O:31])=[CH2:28].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)CC>[C:26]([C:27](=[CH:28][C:22]1[CH:21]=[CH:20][C:19]([O:24][CH3:25])=[CH:18][C:17]=1[CH2:16][N:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:29][C:30]([O:32][CH3:33])=[O:31])([O:35][CH3:36])=[O:34]

Participants

7

Reactant 4

HCID 69240Dimethyl itaconateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 226321523-Bis(tert-butoxycarbonyl)aminomethyl-4-bromoanisole

Product 1

HCID 54374080Methyl (+)-3-carbomethoxy-4-[2-bis(tert-butoxycarbonyl)aminomethyl-4-methoxyphenyl]-3-butenoateYield 66.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

A 500 mL flask was charged with 3-bis(tert-butoxycarbonyl)aminomethyl-4-bromoanisole(15 g, 36 mmol), dimethyl itaconate (7.5 g, 47 mmol), tri-o-tolylphosphine (1 g, 3 mol), palladium acetate (0.4 g, 2 mmol), diisopropylethylamine (12.8 mL, 72 mmol), and propionitrile (150 mL). The mixture was purged with argon (several evacuation/argon flush cycles), then was heated to reflux under argon for 1 hr. The reaction was allowed to cool to RT, then was poured into ice-cold ethyl ether (500 mL). The resulting precipitate was removed by filtration and the filtrate was concentrated. The residue was purified by chromatography on silica gel (10%-20% ethyl acetate in hexane) to give the title compound (11.8 g, 66%) as a pale yellow oil: 1H NMR (CDCl3) δ 7.94 (s, 1 H, 7.15 (d, J=8.1 Hz, 1 H), 6.77 (d, J=8.1 Hz, 1 H, 6.76 (s, 1 H, 4.73 (s, 2 H), 3.81 (s, 3 H), 3.79 (s, 3 H), 3.71 (s, 3 H), 3.38 (s, 2 H), 1.45 (s, 18 H).

Workup

  1. customThe mixture was purged with argon (several evacuation/argon flush cycles)
  2. temperaturewas heated
  3. temperatureto reflux under argon for 1 hr
  4. additionwas poured into ice-cold ethyl ether (500 mL)
  5. customThe resulting precipitate was removed by filtration
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by chromatography on silica gel (10%-20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-54a499255a29425e9f997ba2f1a4c979
Source dataset
uspto-grants-2004_11
Patent number
US06825188B2

Reaction notes

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