Lithium Hydroxide → HCID 21921783, compound

HRID 1245119Notes

Reaction equation

HRID 1245119 reaction equation
C[O:2][C:3](=[O:43])[CH:4]([NH:25][C:26](=[O:42])[C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[N:34]1[CH2:39][CH:38]([CH3:40])[CH2:37][CH:36]([CH3:41])[CH2:35]1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:8][CH:7]=1.[Li+].[OH-]>C1COCC1>[Cl:33][C:31]1[CH:30]=[CH:29][C:28]([N:34]2[CH2:39][CH:38]([CH3:40])[CH2:37][CH:36]([CH3:41])[CH2:35]2)=[C:27]([CH:32]=1)[C:26]([NH:25][CH:4]([CH2:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:10][CH:11]=1)[C:3]([OH:43])=[O:2])=[O:42]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 69609940HCID 69609940, compound

Product 1

HCID 21921783HCID 21921783, compoundYield 93.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-chloro-2-(3,5-dimethyl-piperidin-1-yl)-benzoic acid (0.250 g, 0.933 mmol) in DMF (4.0 mL) was reacted with (2S)-amino-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester hydrochloride (0.360 g, 0.933 mmol), HBTU (0.355 g, 0.933 mmol), and DIEA (0.500 mL, 2.800 mmol) by the general procedure A. The crude product was purified by flash column chromatography on silica gel using DCM (+20% hexane) to give 0.435 g (62%) of 2-[5-Chloro-2-(3,5-dimethyl-piperidin-1-yl)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester. A solution of this ester (0.200 g, 0.334 mmol) in THF (4.0 mL) was reacted with LiOH (0.050 g, 1.172 mmol) by the general procedure I to give 0.182 g (93%) of 2-[5-Chloro-2-(3,5-dimethyl-piperidin-1-yl)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid as a white solid. LCMS: 584 (M+1)+. 1H NMR (CDCl3) 11.20 [d, 1H], 8.21 [d, 1H], 7.45 [m, 2H], 7.39 [m, 2H], 7.23 [m, 8H], 7.02 [m, 2H], 6.86 [m, 2H], 4.90 [m, 1H], 3.38 [dd, 5.60 Hz, 1H], 3.26 [dd, 1H], 2.80 [m, 2H], 2.16 [t, 1H], 2.04 [t, 1H], 1.70 [m, 2H], 1.43 [m, 1H], 0.76 [m, 6H], 0.58 [m, 1H].

Sources & evidence

ORD record
ord-0dadac076d2a4f97b36360be5397c4c1
Source dataset
uspto-grants-2006_10
Patent number
US07122580B2

Reaction notes

Loading…