Lithium Hydroxide → HCID 71455703, compound

HRID 631927Notes

Reaction equation

HRID 631927 reaction equation
C[O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4[N:21]=[N:22][N:23]([CH3:37])[C:24]=4[NH:25][C:26]([O:28][C@@H:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH3:30])=[O:27])=[C:16]([F:38])[CH:15]=3)=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4].O1CCCC1.[Li+].[OH-]>CO>[F:38][C:16]1[CH:15]=[C:14]([C:11]2[CH:10]=[CH:9][C:8]([C:5]3([C:3]([OH:4])=[O:2])[CH2:7][CH2:6]3)=[CH:13][CH:12]=2)[CH:19]=[CH:18][C:17]=1[C:20]1[N:21]=[N:22][N:23]([CH3:37])[C:24]=1[NH:25][C:26]([O:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30])=[O:27]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 72704619HCID 72704619, compound

Product 1

HCID 71455703HCID 71455703, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

In a 250 ml, round-bottomed flask, 1-{3′-fluoro-4′-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazole-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid methyl ester (95 mg, 185 μmol) was combined with tetrahydrofuran (5 mL) and methanol (1.5 mL) to give a light yellow solution. 1M LiOH (1.85 mL, 1.85 mmol, Eq: 10) was added and the reaction was stirred at 25° C. for 22 h. The crude reaction mixture was concentrated in vacuo, acidified with 1M HCl and extracted with dichloromethane. The aqueous layer was back-extracted with dichloromethane (1×15 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 10% methanol in dichloromethane) to afford 85 mg (92%) of the desired product as a white powder. (M+H)′=501.1 (m/e). 1H NMR (DMSO-d6) δ ppm 12.39 (br. s., 1H), 9.92 (br. s., 1H), 7.64-7.78 (m, 3H), 7.59 (d, J=7.8 Hz, 2H), 7.37-7.50 (m, 5H), 7.02-7.37 (m, 2H), 5.74 (br. s., 1H), 3.89 (s, 3H), 1.41-1.60 (m, 4H), 1.09-1.32 (m, 3H).

Workup

  1. customto give a light yellow solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. extractionextracted with dichloromethane
  5. extractionThe aqueous layer was back-extracted with dichloromethane (1×15 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 24 g, 0% to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-39e0e657324b466e978588098a48ab85
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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