Methyl Acrylate → (E)-3-{1'-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-6-yl}-acrylic acid methyl ester

HRID 2046704Notes

Reaction equation

HRID 2046704 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2([NH:18][C:17](=[O:19])[C:16]3[CH:20]=[C:21](Br)[CH:22]=[CH:23][C:15]=3[O:14]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:25]([O:29][CH3:30])(=[O:28])[CH:26]=[CH2:27]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:30][O:29][C:25](=[O:28])/[CH:26]=[CH:27]/[C:21]1[CH:22]=[CH:23][C:15]2[O:14][C:11]3([CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]3)[NH:18][C:17](=[O:19])[C:16]=2[CH:20]=1

Participants

6

Reactant 2

HCID 7294Methyl AcrylateHCID 2794762tert-Butyl 6-bromo-4-oxo-3,4-dihydro-1'H-spiro[1,3-benzoxazine-2,4'-piperidine]-1'-carboxylate

Product 1

HCID 66932321(E)-3-{1'-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-6-yl}-acrylic acid methyl esterYield 99.6%

Reagents, catalysts & solvents 3

HCID 80271Tri-o-tolylphosphineCatalyst2×HCID 167845palladium(II) acetateCatalyst2×HCID 6228DimethylformamideSolvent

Procedure

6-Bromo-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-1′-carboxylic acid tert-butyl ester (5.00 g, 12.6 mmol) was dissolved in hot DMF (15 ml) and then TEA (5.26 ml, 37.8 mmol), tris(o-tolyl)phosphine (153 mg, 0.504 mmol), Pd(OAc)2 (56 mg, 0.25 mmol) and methyl acrylate (3.25 g, 37.8 mmol) were added at RT. The mixture was heated at 100° C. for 6 h under N2 with a further addition of tris(o-tolyl)phosphine (153 mg, 0.504 mmol) and Pd(OAc)2 (56 mg, 0.25 mmol) after three hours) and then partitioned between brine and AcOEt. The organic phase was rinsed with water and brine, dried over Na2SO4 and evaporated. The residue was triturated in AcOEt and petroleum ether to give (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (5.05 g)

Workup

  1. customthen partitioned between brine and AcOEt
  2. washThe organic phase was rinsed with water and brine
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customThe residue was triturated in AcOEt

Sources & evidence

ORD record
ord-17dbd9616b62418da5801a7c02c9d9b9
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

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