Lithium Hydroxide → (2S)-2-[(benzyloxy)carbonyl]amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoic Acid

HRID 724660Notes

Reaction equation

FC(F)(F)C(O)=O.[NH2:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[S:25](=[O:27])(=[O:26])[NH:24][C:23](=[O:28])[CH2:22]2)=[C:17]([Br:29])[CH:16]=1)[C:10]([O:12]C)=[O:11].C(N(CC)CC)C.Cl[C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39].[OH-].[Li+]>CO>[CH2:41]([O:40][C:38]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[S:25](=[O:27])(=[O:26])[NH:24][C:23](=[O:28])[CH2:22]2)=[C:17]([Br:29])[CH:16]=1)[C:10]([OH:12])=[O:11])=[O:39])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Methyl (2S)-2-amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-propanoate trifluoroacetate (83.8 mg, 0.166 mmol) in methanol (2.0 mL) was treated with triethylamine (92.5 μL, 0.663 mmol) and chilled to 0° C. Benzyl chloroformate (20.8 μL, 0.146 mmol) was added and the solution stirred 2 h at 0° C. Aqueous lithium hydroxide solution (4.0 M, 0.21 mL) was added and the solution stirred 2 h. Purification by preparative LCMS afford product as a white solid (69 mg, 81%). 1H NMR (400 MHz, CDCl3): δ 7.48 (brs, 1H), 7.46–7.43 (m, 1H), 7.31–7.26 (m, 6H), 5.65 (t, J=8.2 Hz, 1H), 5.03 (s, 2H), 4.45–4.41 (m, 1H), 3.45 (dd, J=17.5, 8.5 Hz, 1H), 3.36–3.19 (m, 2H), (2.94 dd, J=14.2, 9.7 Hz, 1H); LCMS found for C20H20BrN2O7S (M+H)+: m/z=511.

Workup

stirringthe solution stirred 2 h
customPurification by preparative LCMS

Sources & evidence

ORD record: ord-522910fed99143fc9475aed16898e872
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07141596B2

Reaction notes

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