4-Methylmorpholine → (8-Tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-en-3-yl)-(4-thiazol-2-ylpiperazin-1-yl)methanone

HRID 1013332Notes

Reaction equation

HRID 1013332 reaction equation
[C:1]([CH:5]1[CH2:17][CH2:16][C:8]2([O:12][N:11]=[C:10]([C:13]([OH:15])=O)[CH2:9]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[S:18]1[CH:22]=[CH:21][N:20]=[C:19]1[N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[C:1]([CH:5]1[CH2:6][CH2:7][C:8]2([O:12][N:11]=[C:10]([C:13]([N:26]3[CH2:27][CH2:28][N:23]([C:19]4[S:18][CH:22]=[CH:21][N:20]=4)[CH2:24][CH2:25]3)=[O:15])[CH2:9]2)[CH2:16][CH2:17]1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9118061-(Thiazol-2-yl)piperazineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579514498-Tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid

Product 1

HCID 11976295(8-Tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-en-3-yl)-(4-thiazol-2-ylpiperazin-1-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid (120 mg, 0.51 mmol), 1-thiazol-2-ylpiperazine (110 mg, 0.51 mmol), 4-methylmorpholine (101 mg, 1.02 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (288 mg, 0.65 mmol) (HBTU) were dissolved in DMF (10 ml) and stirred overnight under a nitrogen atmosphere at RT. The solvent was removed under vacuum, the residue taken up in EtOAc and sat. aq. NaHCO3 solution and the phases were separated. The aqueous phase was extracted several times with EtOAc and the combined organic phases were washed with sat. aq. NaCl solution, dried over magnesium sulphate and the solvent was removed under vacuum. After purification by column chromatography (silica gel, hexane/EtOAc 3:1), the desired product (8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-en-3-yl)-(4-thiazol-2-ylpiperazin-1-yl)methanone was obtained as a trans isomer (50 mg, 26% of the theoretical amount) and as a cis isomer (100 mg, 51% of the theoretical amount).

Workup

  1. customThe solvent was removed under vacuum
  2. customsat. aq. NaHCO3 solution and the phases were separated
  3. extractionThe aqueous phase was extracted several times with EtOAc
  4. washthe combined organic phases were washed with sat. aq. NaCl solution
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent was removed under vacuum
  7. customAfter purification by column chromatography (silica gel, hexane/EtOAc 3:1)

Sources & evidence

ORD record
ord-95fa3790bfeb4eb39912f325f12144a3
Source dataset
uspto-grants-2011_07
Patent number
US07981883B2

Reaction notes

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