Methanol → HCID 59822067, compound

HRID 2063337Notes

Reaction equation

HRID 2063337 reaction equation
C([O:5][C:6]([C:8]1[CH:9]=[C:10]2[C:23](=[CH:24][CH:25]=1)[C@@H:22]1[C@H:13]([C@H:14]3[C@@:18]([CH2:20][CH2:21]1)([CH3:19])[C:17]([F:27])([F:26])[CH2:16][C@@H:15]3[CH2:28][CH2:29][CH2:30][C:31]([N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1)=[O:32])[CH2:12][CH2:11]2)=[O:7])CCC.[Li+].[OH-].CO>O>[N:33]1([C:31](=[O:32])[CH2:30][CH2:29][CH2:28][C@@H:15]2[C@H:14]3[C@H:13]4[C@H:22]([CH2:21][CH2:20][C@:18]3([CH3:19])[C:17]([F:26])([F:27])[CH2:16]2)[C:23]2[C:10](=[CH:9][C:8]([C:6]([OH:7])=[O:5])=[CH:25][CH:24]=2)[CH2:11][CH2:12]4)[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 3939Lithium Hydroxide2×HCID 69232892HCID 69232892, compound

Product 1

HCID 59822067HCID 59822067, compoundYield 26.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent4×

Conditions

Temperature
50 °C

Procedure

796 mg 15α-(4-morpholin-4-yl-4-oxobutyl)-17,17-difluoro-estra-1(10),2,4-triene-3-carboxylic acid butyl ester and 5 eq LiOH are mixed with 30 ml MeOH and 10 ml H2O and stirred at 50° C. (water bath) for about 4 h. Then a few mg LiOH, 30 ml MeOH and 10 ml H2O were added and the reaction mixture was stirred for another 2 h at 50° C. After reducing the solvents, H2O is added, the reaction mixture is extracted with EtOAc. The combined aquatic layers are acidified with KHSO4aq to pH 2-3, and extracted twice with EtOAc. The latter organic layers are combined, washed with brine, dried (Na2SO4) and the solvent removed. Purifying by column chromatography (CH2Cl2: MeOH:AcOH 37:3:0.1) give 191 mg of pure 15α-(4-morpholin-4-yl-4-oxobutyl)-17,17-difluoro-estra-1(10),2,4-triene-3-carboxylic acid (=EXAMPLE 7, for NMR see below). 15α-(4-morpholin-4-yl-4-oxobutyl)-17,17-difluoro-estra-1(10),2,4-triene-3-carboxamide

Workup

  1. additionis added
  2. extractionthe reaction mixture is extracted with EtOAc
  3. extractionextracted twice with EtOAc
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. customthe solvent removed
  7. customPurifying by column chromatography (CH2Cl2: MeOH:AcOH 37:3:0.1)

Sources & evidence

ORD record
ord-93b1341206e14f489181607b276863eb
Source dataset
uspto-grants-2012_10
Patent number
US08288367B2

Reaction notes

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