Triphenylphosphine → (R)-2-(5-{3-[5-(4-ethyl-thiazol-2-yl)-pyridin-2-yloxy]-propoxy}-indol-1-yl)-propionic acid methyl ester

HRID 2424978Notes

Reaction equation

[CH2:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][OH:18])=[N:12][CH:13]=2)[S:6][CH:7]=1)[CH3:2].[CH3:19][O:20][C:21](=[O:34])[C@H:22]([N:24]1[C:32]2[C:27](=[CH:28][C:29](O)=[CH:30][CH:31]=2)[CH:26]=[CH:25]1)[CH3:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>ClCCl>[CH3:19][O:20][C:21](=[O:34])[C@H:22]([N:24]1[C:32]2[C:27](=[CH:28][C:29]([O:18][CH2:17][CH2:16][CH2:15][O:14][C:11]3[CH:10]=[CH:9][C:8]([C:5]4[S:6][CH:7]=[C:3]([CH2:1][CH3:2])[N:4]=4)=[CH:13][N:12]=3)=[CH:30][CH:31]=2)[CH:26]=[CH:25]1)[CH3:23]

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 3-[5-(4-ethyl-thiazol-2-yl)-pyridin-2-yloxy]-propan-1-ol (Example 73, 7.0 g, 0.025 mol), (R)-2-(5-hydroxy-indol-1-yl)-propionic acid methyl ester (Example 8, 4.961 g, 0.023 mol), and triphenylphosphine (7.716 g, 0.029 mol) in dichloromethane (60 mL) was treated with a solution of 1,1′-(azodicarbonyl)-dipiperidine (7.423 g, 0.029 mol) in dichloromethane (45 mL) slowly over 25 minutes while maintaining the temperature around 25° C. The resulting suspension was stirred at rt for 18 h. Upon completion, the solvent was removed under vacuum and the crude product was purified by silica gel chromatography using a gradient of 5-35% ethyl acetate/hexanes to give 7.3 g (69%) of the title compound as a beige solid. The product was characterized as in Example 69.

Workup

customUpon completion, the solvent was removed under vacuum
customthe crude product was purified by silica gel chromatography

Sources & evidence

ORD record: ord-e98110fc3d364912a7b48177f363209c
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07964622B2

Reaction notes

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