Methanol → 9-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol

HRID 1972472Notes

Reaction equation

HRID 1972472 reaction equation
[N+](C1SC(S([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][C:21]([C:24]([OH:33])([C:29]([F:32])([F:31])[F:30])[C:25]([F:28])([F:27])[F:26])=[CH:20][N:19]=3)[C@@H:14]([CH2:34][N:35]3[CH:40]4[CH2:41][CH:42]([OH:44])[CH2:43][CH:36]3[CH2:37][O:38][CH2:39]4)[CH2:13]2)(=O)=O)=CC=1)([O-])=O.[N+](C1SC(S([N:56]2[CH2:61][CH2:60][N:59]([C:62]3[N:67]=[CH:66][C:65]([C:68]([OH:77])([C:73]([F:76])([F:75])[F:74])[C:69]([F:72])([F:71])[F:70])=[CH:64][N:63]=3)[C@@H:58]([CH2:78][N:79]3[CH:84]4[CH2:85][C:86](=[O:88])[CH2:87][CH:80]3[CH2:81][O:82][CH2:83]4)[CH2:57]2)(=O)=O)=CC=1)([O-])=O.[OH-].[K+].CO>O>[F:32][C:29]([F:30])([F:31])[C:24]([C:21]1[CH:20]=[N:19][C:18]([N:15]2[CH2:16][CH2:17][NH:12][CH2:13][C@@H:14]2[CH2:34][N:35]2[CH:36]3[CH2:43][CH:42]([OH:44])[CH2:41][CH:40]2[CH2:39][O:38][CH2:37]3)=[N:23][CH:22]=1)([OH:33])[C:25]([F:26])([F:27])[F:28].[F:76][C:73]([F:74])([F:75])[C:68]([C:65]1[CH:64]=[N:63][C:62]([N:59]2[CH2:60][CH2:61][NH:56][CH2:57][C@@H:58]2[CH2:78][N:79]2[CH:80]3[CH2:87][C:86](=[O:88])[CH2:85][CH:84]2[CH2:83][O:82][CH2:81]3)=[N:67][CH:66]=1)([OH:77])[C:69]([F:70])([F:72])[F:71]

Participants

7

Reactant 4

HCID 887MethanolHCID 14797Potassium HydroxideHCID 866703529-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-olHCID 866703539-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

Product 2

HCID 866703549-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-olHCID 866703559-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 25-mL round-bottomed flask was charged with a 1:1 mixture of 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (300 mg, 0.44 mmol, Example 98, Step 5), potassium hydroxide (749 mg, 13.34 mmol), MeOH (5 mL) and water (2 mL) and was stirred at room temperature for 30 min. The solvent was removed in vacuo and then diluted with water (50 mL) and extracted with EtOAc (3×50 mL). The organic layers were dried (Na2SO4), filtered, and concentrated to give 9-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (215 mg) which were used without purification.

Workup

  1. customThe solvent was removed in vacuo
  2. additiondiluted with water (50 mL)
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialThe organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-bce106984a54402a80ef58ea7bb58892
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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