1,2-Dimethoxyethane → (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(4-iodophenyl)propanoic acid

HRID 1503651Notes

Reaction equation

C([N:8]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([I:17])=[CH:13][CH:12]=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(COC)OC>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:21]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([I:17])=[CH:15][CH:16]=1)([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22]

Participants

Conditions

Temperature: 80 °C

Procedure

Benzyl Boc-4-iodophenylalanine (1 eq.), arylboronic acid (1.5 eq.), sodium carbonate (2 eq.), palladium acetate (0.05 eq.) and tri ortho-tolylphosphine (0.1 eq.) was added to a degassed mixture of dimethoxyethane (6 ml/mmol amino acid) and water (1 ml/mmol amino acid). The reaction mixture was kept under argon and heated to 80° C. for 4-6 h. After cooling to room temperature, the mixture was filtered through a short pad of silica gel and sodium carbonate. The filter cake was further washed with ethyl acetate and combined with the other fraction before the solvents were removed under reduced pressure. The products were purified using flash chromatography using mixtures of ethyl acetate and n-hexane as eluent.

Workup

temperatureAfter cooling to room temperature
filtrationthe mixture was filtered through a short pad of silica gel and sodium carbonate
washThe filter cake was further washed with ethyl acetate
customwere removed under reduced pressure
customThe products were purified

Sources & evidence

ORD record: ord-bbca764cd96d4fe4a5a017886a95261e
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212202B2

Reaction notes

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