Phenylacetaldehyde → HCID 66932261, compound

HRID 2046761Notes

Reaction equation

HRID 2046761 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:23])/[CH:5]=[CH:6]/[C:7]1[CH:8]=[CH:9][C:10]2[O:20][C:14]3([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[NH:13][C:12](=[O:21])[C:11]=2[CH:22]=1.[OH-].[Na+].[C:26]1([CH2:32][CH:33]=O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[BH3-]C#N.[Na+]>CO.CC(O)=O>[CH3:2][O:3][C:4](=[O:23])/[CH:5]=[CH:6]/[C:7]1[CH:8]=[CH:9][C:10]2[O:20][C:14]3([CH2:19][CH2:18][N:17]([CH2:33][CH2:32][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:16][CH2:15]3)[NH:13][C:12](=[O:21])[C:11]=2[CH:22]=1

Participants

7

Reactant 4

HCID 998PhenylacetaldehydeHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 66932407HCID 66932407, compound

Product 1

HCID 66932261HCID 66932261, compoundYield 89.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

(E)-3-{3,4-Dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester hydrochloride (obtained as described in Example 25, Step B, 300 mg, 0.886 mmol) was dissolved in MeOH (30 ml). The pH was adjusted to 5 with AcOH and 1 M NaOH in MeOH, and then phenyl-acetaldehyde (128 mg, 1.06 mmol) and NaCNBH3 (67 mg, 1.06 mmol) were added. The mixture was stirred overnight at RT, then the solvent was removed and the residue partitioned between 5% aqueous NaHCO3 and DCM. The organic phase was dried over Na2SO4 and evaporated. The crude product was purified by column chromatography (eluent:DCM/MeOH 95:5) to give (E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (322 mg).

Workup

  1. customthe solvent was removed
  2. customthe residue partitioned between 5% aqueous NaHCO3 and DCM
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customevaporated
  5. customThe crude product was purified by column chromatography (eluent:DCM/MeOH 95:5)

Sources & evidence

ORD record
ord-69aab621bd08496b861cf409488a70ae
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

Loading…