Sodium t-butoxide → Trifluoroacetic acid

HRID 713266Notes

Reaction equation

HRID 713266 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[CH2:8]([N:15]1[CH:24]([CH3:25])[CH2:23][C:22]2[C:17](=[N:18][C:19](Cl)=[C:20]([NH:26][CH2:27][CH:28]([F:30])[F:29])[N:21]=2)[CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl.[F:33][C:34]1[CH:46]=[C:45]([F:47])[CH:44]=[CH:43][C:35]=1[O:36][CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.CC(C)([O-])C.[Na+]>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>[CH2:8]([N:15]1[CH:24]([CH3:25])[CH2:23][C:22]2[C:17](=[N:18][C:19]([N:40]3[CH2:39][CH2:38][CH:37]([O:36][C:35]4[CH:43]=[CH:44][C:45]([F:47])=[CH:46][C:34]=4[F:33])[CH2:42][CH2:41]3)=[C:20]([NH:26][CH2:27][CH:28]([F:30])[F:29])[N:21]=2)[CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

9

Reactant 3

HCID 23676156Sodium t-butoxideHCID 429489434-(2,4-Difluorophenoxy)piperidine hydrochlorideHCID 1317340236-benzyl-3-chloro-N-(2,2-difluoroethyl)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

Product 2

HCID 6422Trifluoroacetic acidYield 460.7%HCID 1181593356-benzyl-N-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxy)piperidin-1-yl)-7-methyl-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 6-benzyl-3-chloro-N-(2,2-difluoroethyl)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (120 mg, 0.257 mmol), 4-(2,4-difluorophenoxyl)piperidine hydrochloride (77 mg, 0.308 mmol), Pd2(dba)3 (23.5 mg, 0.026 mmol), BINAP (32.0 mg, 0.051 mmol), and sodium tert-butoxide (74.1 mg, 0.771 mmol), in toluene (1.28 mL) was stirred at 100° 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-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine as a TFA salt (135 mg, 82%).

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-a5e130aa34c74027a4b9e5b44f1bbf77
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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