Sodium t-butoxide → Trifluoroacetic acid

HRID 713256Notes

Reaction equation

HRID 713256 reaction equation
CC(C)([O-])C.[Na+].[OH:7][C:8]([C:10]([F:13])([F:12])[F:11])=[O:9].[CH2:14]([N:21]1[CH2:30][CH2:29][C:28]2[C:23](=[N:24][C:25](Cl)=[C:26]([NH:31][C:32]([CH3:35])([CH3:34])[CH3:33])[N:27]=2)[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl.[F:38][C:39]1[CH:51]=[C:50]([F:52])[CH:49]=[CH:48][C:40]=1[O:41][CH:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1>C1(C)C=CC=CC=1.CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH2:14]([N:21]1[CH2:30][CH2:29][C:28]2[C:23](=[N:24][C:25]([N:45]3[CH2:44][CH2:43][CH:42]([O:41][C:40]4[CH:48]=[CH:49][C:50]([F:52])=[CH:51][C:39]=4[F:38])[CH2:47][CH2:46]3)=[C:26]([NH:31][C:32]([CH3:35])([CH3:34])[CH3:33])[N:27]=2)[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C:8]([OH:9])([C:10]([F:13])([F:12])[F:11])=[O:7]

Participants

9

Reactant 3

HCID 23676156Sodium t-butoxideHCID 429489434-(2,4-Difluorophenoxy)piperidine hydrochlorideHCID 1317340166-benzyl-N-(tert-butyl)-3-chloro-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

Product 2

HCID 6422Trifluoroacetic acidYield 483.8%HCID 1181592786-benzyl-N-(tert-butyl)-3-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine

Reagents, catalysts & solvents 4

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of sodium tert-butoxide (81 mg, 0.843 mmol), 6-benzyl-N-(tert-butyl)-3-chloro-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (125 mg, 0.281 mmol), Pd2(dba)3 (12.86 mg, 0.014 mmol), 4-(2,4-difluorophenoxyl)piperidine hydrochloride (84 mg, 0.337 mmol), and BINAP (17.50 mg, 0.028 mmol) in toluene (937 μL) was stirred at 90° C. overnight. The crude reaction mixture was diluted in DMF, filtered through a hydrophilic PTFE 0.45 μm filter (Millipore® Millex-LCR), and purified via HPLC Method A to give 6-benzyl-N-(tert-butyl)-3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine as a TFA salt (155 mg).

Workup

  1. customThe crude reaction mixture
  2. filtrationfiltered through a hydrophilic PTFE 0.45 μm
  3. filtrationfilter (Millipore® Millex-LCR)
  4. custompurified via HPLC Method A

Sources & evidence

ORD record
ord-7295972bb4924c94a95f7b2c97f1bcfa
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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