Sodium Carbonate → (2S)-2-[(benzyloxy)carbonyl]amino-3-[6-(1,1-dioxido-3-oxoisothiazolidin-5-yl)biphenyl-3-yl]propanoic Acid

HRID 724691Notes

Reaction equation

[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]2[S:28](=[O:30])(=[O:29])[NH:27][C:26](=[O:31])[CH2:25]2)=[C:20](Br)[CH:19]=1)[C:13]([O:15]C)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1.O.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>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:17][C:18]1[CH:19]=[C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:21]([CH:24]2[S:28](=[O:30])(=[O:29])[NH:27][C:26](=[O:31])[CH2:25]2)=[CH:22][CH:23]=1)[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of methyl (2S)-2-[(benzyloxy)carbonyl]amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoate (52.0 mg, 0.0990 mmol) in toluene (1.0 mL) and 1,4-dioxane (1.0 mL) was added phenylboronic acid (14.5 mg, 0.119 mmol), 2 M sodium carbonate in water (0.30 mL) and tetrakis(triphenylphosphine)palladium(0) (6 mg, 0.005 mmol) under an atmosphere of nitrogen. The resulting mixture was heated at 100° C. overnight. The reaction solution was filtered, and purified by preparative LCMS to afford product as a white solid (18 mg, 38%). 1H NMR (400 MHz, CD3OD): δ 7.28 (m, 13H), 5.03 (m, 1H), 4.47 (m, 1H), 3.26 (m, 3H), 3.00 (m, 1H). LCMS found for C26H25N2O7S (M+H)+: m/z=509.

Workup

filtrationThe reaction solution was filtered
custompurified by preparative LCMS

Sources & evidence

ORD record: ord-03299033ac19426a87dc5e3ba80b6f34
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07141596B2

Reaction notes

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