Hydrochloric Acid → (R)-tert-Butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acid

HRID 2222977Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:22][C:23]1([CH3:34])[O:27][C@@H:26]([CH2:28]OS(C)(=O)=O)[CH2:25][O:24]1.Cl>CN(C)C=O.O.C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:28][C@H:26]2[CH2:25][O:24][C:23]([CH3:34])([CH3:22])[O:27]2)=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 100 °C

Procedure

(R)-tert-Butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (200 mg, 0.75 mmol) was dissolved in anhydrous N,N-dimethylformamide (4 mL) followed by the addition of sodium hydride (60% dispersion in mineral oil) (63 mg, 1.57 mmol) at room temperature. The reaction was stirred for 30 minutes followed by the dropwise addition of methanesulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan4-ylmethyl ester (189 mg, 0.90 mmol) dissolved in N,N-dimethylformamide (2 mL) at room temperature. The mixture was heated to 100° C. overnight. The reaction was cooled to room temperature, acidified to pH=4 with 0.2 M aqueous hydrochloric acid, poured into ethyl acetate and diluted with water. The organic layer was washed with brine and dried over sodium sulfate. Removal of solvents gave (R)-tert-butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan4-ylmethoxy)-phenyl]-acetic acid as a foam (280 mg, 98%).

Workup

temperatureThe reaction was cooled to room temperature
washThe organic layer was washed with brine
dry with materialdried over sodium sulfate
customRemoval of solvents

Sources & evidence

ORD record: ord-d379e27d89954e279f381fb225adf0cc
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07371869B2

Reaction notes

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