Sulfuric Acid → (2R,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one sulfuric acid salt

HRID 2207701Notes

Reaction equation

HRID 2207701 reaction equation
[CH3:1][N:2]1[CH2:27][CH2:26][C:4]2([NH:8][CH:7]([C:9]3[N:14]=[C:13]([CH3:15])[CH:12]=[C:11]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=4)[N:10]=3)[CH2:6][CH2:5]2)[C:3]1=[O:28].[S:29](=[O:33])(=[O:32])([OH:31])[OH:30]>CC#N>[S:29](=[O:31])(=[O:30])([OH:33])[OH:32].[CH3:1][N:2]1[CH2:27][CH2:26][C@:4]2([NH:8][C@@H:7]([C:9]3[N:14]=[C:13]([CH3:15])[CH:12]=[C:11]([C:16]4[CH:17]=[CH:18][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:20][CH:21]=4)[N:10]=3)[CH2:6][CH2:5]2)[C:3]1=[O:28]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 725484337-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one

Product 1

HCID 72548434(2R,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one sulfuric acid salt

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A similarly prepared sample was recrystallised from diethyl ether and isohexane to give the free base form of the title material as a colorless solid with a melting point of 66-67° C. Similarly prepared 7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one with a diastereomeric excess of approximately 92% (49 g, 125.51 mmol) in MeCN (700 mL) was suction filtered through a shallow pad of Hyflo to give a clear yellow solution. To this rapidly stirred solution at 50° C. was added 7.5M sulphuric acid (17.6 mL, 132 mmol) over 5 seconds to give a solution which quickly crystallized. The mixture was left to stand at ambient temperature for 2 h then filtered and washed with acetonitrile/Et2O (1:1) (200 ml) then Et2O (150 ml) and dried 50° C. to give the title material (E2) in an 82:1 ratio of (2R,5S) and (2S,5S) isomers (50.6 g) assessed by NMR.

Workup

  1. customA similarly prepared sample was recrystallised from diethyl ether and isohexane
  2. customto give the free base form of the title material as a colorless solid with a melting point of 66-67° C
  3. filtrationfiltered through a shallow pad of Hyflo
  4. customto give a clear yellow solution
  5. customto give a solution which
  6. customquickly crystallized
  7. waitThe mixture was left
  8. filtrationthen filtered
  9. washwashed with acetonitrile/Et2O (1:1) (200 ml)
  10. dry with materialEt2O (150 ml) and dried 50° C.

Sources & evidence

ORD record
ord-343b6a0a66cf43ddbedbc3a1096c674b
Source dataset
uspto-grants-2016_06
Patent number
US09376445B2

Reaction notes

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