Sodium t-butoxide → Trifluoroacetic acid

HRID 713254Notes

Reaction equation

HRID 713254 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[CH2:8]([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[N:18][C:19](Cl)=[C:20]([NH:25][CH2:26][CH:27]([F:29])[F:28])[N:21]=2)[CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl.[F:32][C:33]1[CH:45]=[C:44]([F:46])[CH:43]=[CH:42][C:34]=1[O:35][CH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.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[CH2:24][CH2:23][C:22]2[C:17](=[N:18][C:19]([N:39]3[CH2:38][CH2:37][CH:36]([O:35][C:34]4[CH:42]=[CH:43][C:44]([F:46])=[CH:45][C:33]=4[F:32])[CH2:41][CH2:40]3)=[C:20]([NH:25][CH2:26][CH:27]([F:29])[F:28])[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

8

Reactant 3

HCID 23676156Sodium t-butoxideHCID 429489434-(2,4-Difluorophenoxy)piperidine hydrochlorideHCID 1317340146-benzyl-3-chloro-N-(2,2-difluoroethyl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

Product 2

HCID 6422Trifluoroacetic acidYield 402.7%HCID 1181591176-benzyl-N-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A solution of 6-benzyl-3-chloro-N-(2,2-difluoroethyl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (150 mg, 0.331 mmol), 4-(2,4-difluorophenoxyl)piperidine hydrochloride (99 mg, 0.398 mmol), Pd2(dba)3 (15.2 mg, 0.017 mmol), BINAP (20.63 mg, 0.033 mmol), and sodium tert-butoxide (96 mg, 0.994 mmol), in toluene (1104 μL) was stirred at 90° C. overnight. The solvent was removed and the crude product 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)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine as a TFA salt (152 mg).

Workup

  1. customThe solvent was removed
  2. additionthe crude product diluted in DMF
  3. filtrationfiltered through a hydrophilic PTFE 0.45 μm
  4. filtrationfilter (Millipore® Millex-LCR)
  5. custompurified via HPLC Method A

Sources & evidence

ORD record
ord-9292b5d2af3a4ef38ecb462be414bab6
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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