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

HRID 518161Notes

Reaction equation

HRID 518161 reaction equation
[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[CH:8][C:9]2[O:26][C:13]3([CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[NH:12][C:11](=[O:27])[C:10]=2[CH:28]=1.[H-].[Na+].[CH3:32]I>CN(C=O)C>[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[CH:8][C:9]2[O:26][C:13]3([CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[N:12]([CH3:32])[C:11](=[O:27])[C:10]=2[CH:28]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66932321(E)-3-{1'-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-6-yl}-acrylic acid methyl ester

Product 1

HCID 66932109(E)-3-{1'-tert-butoxycarbonyl-3,4-dihydro-3-methyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-6-yl}-acrylic acid methyl esterYield 87.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(E)-3-{1′-Tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (4.02 g, 10.0 mmol) was dissolved in DMF (35 ml) and added to a stirred suspension of NaH (60% oil dispersion, 480 mg, 12 mmol) in DMF (35 ml) at 4° C. After 10 min CH3I (2.13 g, 15.0 mmol) was added, the resulting mixture was stirred at RT for 30 min and then partitioned between saturated aqueous solution of NH4Cl and AcOEt. The organic phase was rinsed with water, dried over Na2SO4 and evaporated. The crude mixture was purified by trituration in AcOEt and petroleum ether to give (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-methyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (3.66 g).

Workup

  1. custompartitioned between saturated aqueous solution of NH4Cl and AcOEt
  2. washThe organic phase was rinsed with water
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customThe crude mixture was purified by trituration in AcOEt

Sources & evidence

ORD record
ord-871c68eee4904888a7f16afee188f8c2
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

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