Hydrochloric Acid → (R)-2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propylthio)acetic acid

HRID 920150Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:30])=[C:6]([C@:8]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=2[O:28][CH3:29])([CH3:17])[CH2:9][S:10][CH2:11][C:12]([O:14]CC)=[O:13])[CH:7]=1.[OH-].[Li+].Cl>O1CCCC1.CO.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:30])=[C:6]([C@:8]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=2[O:28][CH3:29])([CH3:17])[CH2:9][S:10][CH2:11][C:12]([OH:14])=[O:13])[CH:7]=1

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of (R)-ethyl 2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propylthio)acetate (3 g, 5.99 mmol, Eq: 1.00) in tetrahydrofuran (20 ml), methanol (10 ml), water (5 ml) was added at 23° C. lithium hydroxide (287 mg, 12.0 mmol, Eq: 2.0). The colourless reaction solution was stirred at 23° C. for 2 hours. The reaction mixture was neutralized with 1 N HCl (12.0 ml, 12.0 mmol, Eq: 2.0) (pH=5-6) and evaporated. The residue was triturated with dichloromethane/methanol 9:1 and solid Na2SO4 was added. The solid was filtered off and the filtrate was evaporated to dryness to give the crude (R)-2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propylthio)acetic acid (3.2 g, 6.1 mmol, 102% yield) as a white foam which was used without further purification. MS (ISN): m/z=470.6 [M−H]− and 472.5 [M+2−H]−.

Workup

customevaporated
customThe residue was triturated with dichloromethane/methanol 9:1 and solid Na2SO4
additionwas added
filtrationThe solid was filtered off
customthe filtrate was evaporated to dryness

Sources & evidence

ORD record: ord-ea584a4700d14327be7789d6cad3c94a
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273042B2

Reaction notes

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