Methanol → HCID 59822064, compound

HRID 2063338Notes

Reaction equation

HRID 2063338 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:20](=[CH:21][CH:22]=1)[C@@H:19]1[C@H:10]([C@H:11]3[C@@:15]([CH2:17][CH2:18]1)([CH3:16])[C:14]([F:24])([F:23])[CH2:13][C@H:12]3[CH2:25][CH2:26][C:27]([NH:29][C:30]1[S:31][C:32]([CH3:35])=[CH:33][N:34]=1)=[O:28])[CH2:9][CH2:8]2)=[O:4].[Li+].[OH-].CO.C1COCC1>O>[F:24][C:14]1([F:23])[CH2:13][C@@H:12]([CH2:25][CH2:26][C:27]([NH:29][C:30]2[S:31][C:32]([CH3:35])=[CH:33][N:34]=2)=[O:28])[C@H:11]2[C@H:10]3[C@H:19]([CH2:18][CH2:17][C@:15]12[CH3:16])[C:20]1[C:7](=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:22][CH:21]=1)[CH2:8][CH2:9]3

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 86623681HCID 86623681, compound

Product 1

HCID 59822064HCID 59822064, compoundYield 8.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Procedure

0.9 g 17,17-difluoro-15beta-{3-[(5-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}estra-1(10),2,4-triene-3-carboxylic acid methyl ester and 0.5 g LiOH are mixed with 30 ml MeOH, 50 ml THF and 30 ml H2O and stirred at 80° C. (water bath) for about 30 min. H2O is added, the reaction mixture is extracted with EtOAc three times. The combined aquatic layers are acidified with KHSO4aq to pH 2-3, and extracted the times with EtOAc. The latter organic layers are combined, washed with brine, dried (Na2SO4) and the solvent removed. 620 mg crude compound was obtained which was used in the following step without further purification. Purifying by column chromatography (CH2Cl2: MeOH:AcOH 37:3:0.1) give 77 mg of pure 17,17-difluoro-15beta-{3-[(5-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}estra-1(10),2,4-triene-3-carboxylic acid (=EXAMPLE 9, NMR spectra see below).

Workup

  1. extractionthe reaction mixture is extracted with EtOAc three times
  2. extractionextracted the times with EtOAc
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. customthe solvent removed
  6. custom620 mg crude compound was obtained which
  7. customwas used in the following step without further purification
  8. customPurifying by column chromatography (CH2Cl2: MeOH:AcOH 37:3:0.1)

Sources & evidence

ORD record
ord-49517aa213424acea4ec5be492d597fb
Source dataset
uspto-grants-2012_10
Patent number
US08288367B2

Reaction notes

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