Phenylacetaldehyde → HCID 66932609, compound

HRID 518203Notes

Reaction equation

HRID 518203 reaction equation
[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][N:14]([C:17](OC(C)(C)C)=O)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:28].C(Cl)Cl.[C:33]1([CH2:39]C=O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[Na]>C([O-])([O-])=O.[K+].[K+]>[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:12][CH2:13][N:14]([CH2:17][CH2:39][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:15][CH2:16]1)[CH2:10][C:9]2=[O:28]

Participants

6

Reactant 4

HCID 998PhenylacetaldehydeHCID 6344DichloromethaneHCID 5360545SodiumHCID 52952087(E)-3-{1'-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester2×

Product 1

HCID 66932609HCID 66932609, compoundYield 71.9%

Reagents, catalysts & solvents 1

HCID 11430Potassium CarbonateSolvent

Procedure

A suspension of (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (2.0 g, 5.9 mmol, Intermediate 1, hydrochloride salt) in 1 M K2CO3 solution (30 ml) was stirred for 10 minutes, then DCM (3×30 ml) was added to extract the corresponding free base. The organic phase was dried and concentrated to 50 ml, then phenylacetaldehyde (0.79 ml, 7.10 mmol) and sodium triacethoxyborohydride (1.88 g, 8.88 mmol) were subsequently added. The mixture was stirred for 3 h, washed with water, and the pH value was adjusted to 8 with aqueous ammonia. The product was extracted with DCM and the organic solution was dried and concentrated. The crude residue was purified by column chromatography (eluent: DCM/MeOH 99:1 to 97:3) to give (E)-3-{1′-(2-phenyl-ethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (1.72 g) as a light yellow solid.

Workup

  1. extractionto extract the corresponding free base
  2. customThe organic phase was dried
  3. concentrationconcentrated to 50 ml
  4. stirringThe mixture was stirred for 3 h
  5. washwashed with water
  6. extractionThe product was extracted with DCM
  7. customthe organic solution was dried
  8. concentrationconcentrated
  9. customThe crude residue was purified by column chromatography (eluent: DCM/MeOH 99:1 to 97:3)

Sources & evidence

ORD record
ord-f4b720b579774a04a02bcc9316305ae8
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

Loading…