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

HRID 2046707Notes

Reaction equation

HRID 2046707 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+].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[NH4+].[Cl-]>CN(C=O)C.O>[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]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:11](=[O:27])[C:10]=2[CH:28]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 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 66932363(E)-3-{1'-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-6-yl}-acrylic acid methyl esterYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

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 (1.8 g, 4.5 mmol, Example 25, Step A) was dissolved in dry DMF (25 ml) under N2, and NaH (268.6 mg, 6.71 mmol, 60% suspension in mineral oil) was added. After 10 min stirring, benzyl bromide (1.07 ml, 8.95 mmol) was added dropwise and the mixture was heated for 3 h at 80° C. The mixture was poured into water and a saturated NH4Cl solution was added. The aqueous phase was extracted with DCM, and the combined organic phases were dried and concentrated. The crude residue was purified by column chromatography (eluent:petroleum ether/AcOEt 90:10 to 70:30) to give (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (1.3 g, 59%) as a white solid.

Workup

  1. extractionThe aqueous phase was extracted with DCM
  2. customthe combined organic phases were dried
  3. concentrationconcentrated
  4. customThe crude residue was purified by column chromatography (eluent:petroleum ether/AcOEt 90:10 to 70:30)

Sources & evidence

ORD record
ord-f41b4b0650974f5895be3f777c0001cd
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

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