4-Methylmorpholine → 8-Tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(4-tert-butylphenyl)amide

HRID 1013330Notes

Reaction equation

HRID 1013330 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].[C:18]([C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19].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:18]([C:22]1[CH:23]=[CH:24][C:25]([NH:26][C:13]([C:10]2[CH2:9][C:8]3([CH2:7][CH2:6][CH:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:17][CH2:16]3)[O:12][N:11]=2)=[O:15])=[CH:27][CH:28]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 698614-Tert-ButylanilineHCID 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 579514578-Tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(4-tert-butylphenyl)amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid (220 mg, 0.91 mmol), 4-tert-butylaniline (137 mg, 0.91 mmol), 4-methylmorpholine (279 mg, 2.76 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (528 mg, 1.20 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 dried over magnesium sulphate and the solvent was removed under vacuum. After purification by column chromatography (silica gel, ether/hexane 2:1), the desired product 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(4-tert-butylphenyl)amide was obtained as a diastereomer mixture in a yield of 80 mg (24% 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. dry with materialthe combined organic phases were dried over magnesium sulphate
  5. customthe solvent was removed under vacuum
  6. customAfter purification by column chromatography (silica gel, ether/hexane 2:1)

Sources & evidence

ORD record
ord-fc2ea5551fa745a3a2adee33886dae7f
Source dataset
uspto-grants-2011_07
Patent number
US07981883B2

Reaction notes

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