Lithium Hydroxide → HCID 44608297, compound

HRID 656765Notes

Reaction equation

HRID 656765 reaction equation
CC(C)(C)C(NC1C=CC(OC2C=C(CC(O)=O)C=CC=2OC)=C(CSCC(F)(F)F)C=1)=O.IC.[H-].[Na+].C[O:39][C:40](=[O:72])[CH2:41][C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[C:44]([O:50][C:51]2[CH:56]=[CH:55][C:54]([N:57]([C:59](=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61])[CH3:58])=[CH:53][C:52]=2[CH2:65][S:66][CH2:67][C:68]([F:71])([F:70])[F:69])[CH:43]=1.[OH-].[Li+]>CC#N.CO.O>[CH3:61][C:60]([CH3:63])([CH3:62])[C:59]([N:57]([CH3:58])[C:54]1[CH:55]=[CH:56][C:51]([O:50][C:44]2[CH:43]=[C:42]([CH2:41][C:40]([OH:72])=[O:39])[CH:47]=[CH:46][C:45]=2[O:48][CH3:49])=[C:52]([CH2:65][S:66][CH2:67][C:68]([F:70])([F:69])[F:71])[CH:53]=1)=[O:64]

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 44600604HCID 44600604, compoundHCID 58372760HCID 58372760, compound

Product 1

HCID 44608297HCID 44608297, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

To {3-[4-(2,2-dimethyl-propionylamino)-2-(2,2,2-trifluoro-ethylsulfanylmethyl)-phenoxy]-4-methoxy-phenyl}-acetic acid (0.128 g, 0.26 mmol) in MeCN (3 mL) was added iodomethane (0.03 mL, 0.53 mmol), followed by sodium hydride (60% in mineral oil; 0.021 g, 0.53 mmol). The reaction was stirred at room temperature, but only starting material was seen by analytical LCMS, so the reaction was heated to 60° C. for 2 hours, and then cooled to room temperature and stirred for 2 days under N2. The mixture was used directly in the hydrolysis step. To a solution of {3-[4-[(2,2-dimethyl-propionyl)-methyl-amino]-2-(2,2,2-trifluoro-ethylsulfanylmethyl)-phenoxy]-4-methoxy-phenyl}-acetic acid methyl ester (0.26 mmol) in MeCN was added H2O, MeOH, and lithium hydroxide, and the reaction was heated to 65° C. for 1 hour to give the title compound.

Workup

  1. temperaturewas heated to 60° C. for 2 hours
  2. temperaturecooled to room temperature
  3. stirringstirred for 2 days under N2
  4. customThe mixture was used directly in the hydrolysis step
  5. temperaturethe reaction was heated to 65° C. for 1 hour

Sources & evidence

ORD record
ord-5ee13f17ffbd4800948da065df87d5f9
Source dataset
uspto-grants-2011_12
Patent number
US08071807B2

Reaction notes

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