Sodium Hydroxide → 4-{(2R)-2-[({(2S)-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl}amino)methyl]-3,4-dihydro-2H-chromen-6-yl}benzoic Acid

HRID 47688Notes

Reaction equation

[CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:15]=[CH:14][C:8]([O:9][CH2:10][C@@H:11]2[CH2:13][O:12]2)=[CH:7][CH:6]=1.[NH2:16][CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:37]=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][CH:29]=3)[CH:24]=2)[O:19]1.[OH-].[Na+]>O1CCOCC1>[OH:12][C@H:11]([CH2:10][O:9][C:8]1[CH:14]=[CH:15][C:5]([CH2:4][CH2:3][O:2][CH3:1])=[CH:6][CH:7]=1)[CH2:13][NH:16][CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:29]=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:36][CH:37]=3)[CH:24]=2)[O:19]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of epoxide (Example 16, 0.25 mmol) in 2 mL of aqueous 1,4-dioxane (10% water) was added methyl 4-[(2R)-2-(aminomethyl)-3,4-dihydro-2H-chromen-6-yl]benzoate (40 mg, 0.13 mmol). The mixture was stirred at 80° C. for 72 hours and allowed to cool to room temperature. When ambient temperature was achieved, 1N aqueous sodium hydroxide (1 mL) was added to the solution at room temperature, and stirring continued for another 0.5 hour. The product was then purified by preparative HPLC (Gradient 0-70% Acetonitrile/0.1% aq. TFA) to obtain 6.7 mg of product (as a TFA salt). MH+492.4 (free base).

Workup

temperatureto cool to room temperature
customWhen ambient temperature
stirringstirring
waitcontinued for another 0.5 hour
customThe product was then purified by preparative HPLC (Gradient 0-70% Acetonitrile/0.1% aq. TFA)

Sources & evidence

ORD record: ord-0846486d44fd4fddbad2b57d35bc9362
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06699860B2

Reaction notes

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