Methanol → HCID 59822071, compound

HRID 2063334Notes

Reaction equation

HRID 2063334 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](=[O:23])[CH2:13][C@H:12]3[CH2:24][CH2:25][C:26]([NH:28][C:29]1[S:30][C:31]([CH3:34])=[CH:32][N:33]=1)=[O:27])[CH2:9][CH2:8]2)=[O:4].[Li+].[OH-].CO>O>[CH3:34][C:31]1[S:30][C:29]([NH:28][C:26](=[O:27])[CH2:25][CH2:24][C@H:12]2[C@H:11]3[C@H:10]4[C@H:19]([CH2:18][CH2:17][C@:15]3([CH3:16])[C:14](=[O:23])[CH2:13]2)[C:20]2[C:7](=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:22][CH:21]=2)[CH2:8][CH2:9]4)=[N:33][CH:32]=1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 3939Lithium Hydroxide2×HCID 86623680HCID 86623680, compound

Product 1

HCID 59822071HCID 59822071, compoundYield 44.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent4×

Conditions

Temperature
50 °C

Procedure

350 mg 15β-{3-[(5-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}-17-oxoestra-1(10),2,4-triene-3-carboxylic acid methyl 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 150 mg pure 15β-{3-[(5-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}-17-oxoestra-1(10),2,4-triene-3-carboxylic acid (=EXAMPLE 4, NMR data see below). 15β-{3-[(5-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}-17-oxoestra-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-dc1b67034721471087a1fc20ef39fc02
Source dataset
uspto-grants-2012_10
Patent number
US08288367B2

Reaction notes

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