Tetrahydro-2H-pyran-4-carboxaldehyde → Ethyl 2-(3-nitrophenyl)-3-(tetrahydropyran-4-yl)acrylate

HRID 729709Notes

Reaction equation

HRID 729709 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[CH:7]=1)[CH3:2].[O:16]1[CH2:21][CH2:20][CH:19]([CH:22]=O)[CH2:18][CH2:17]1>>[N+:12]([C:8]1[CH:7]=[C:6]([C:5](=[CH:22][CH:19]2[CH2:20][CH2:21][O:16][CH2:17][CH2:18]2)[C:4]([O:3][CH2:1][CH3:2])=[O:15])[CH:11]=[CH:10][CH:9]=1)([O-:14])=[O:13]

Participants

3

Reactant 2

HCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 14997011Ethyl (3-nitrophenyl)acetate

Product 1

HCID 67487895Ethyl 2-(3-nitrophenyl)-3-(tetrahydropyran-4-yl)acrylate

Procedure

Ethyl(3-nitrophenyl)acetate (11.60 g, 55.5 mmol) was condensed with tetrahydropyran-4-carboxaldehyde employing the procedure described in Preparation 30 to give ethyl 2-(3-nitrophenyl)-3-(tetrahydropyran-4-yl)acrylate: m/z (ES+)=628.3 [2M+NH4]+. A solution of this compound (4.65 g, 15.2 mmol) in EtOH (80 mL) was treated with a slurry of Pd (10% on C, 49 mg, 0.46 mmol) in EtOH (10 mL) and H2O (1 mL). The mixture was stirred under a H2 atmosphere for 24 h, before being filtered through Celite. The Celite was washed with EtOAc (5×50 mL), then the combined filtrates were evaporated to give ethyl 2-(3-aminophenyl)-3-(tetrahydropyran-4-yl)propionate: m/z (ES+)=278.2 [M+H]+. A solution of this compound (2.77 g, 10.0 mmol) in DME (10 mL) was added over 30 min to a stirred mixture of i-AmONO) (2.0 mL, 15.0 mmol) and MeSSMe (9.9 mL, 110.0 mmol). The temperature was raised to 45° C. for 0.5 h and then to 85° C. for 1.5 h. On cooling, the solvents were removed under reduced pressure, then the residue was dissolved in EtOAc (60 mL). The EtOAc solution was washed with 1M HCl (2×20 mL), H2O (20 mL), and brine (20 mL). Filtration, solvent evaporation, and column chromatography (CH2Cl2-Et2O, 1:0 to 99:1) afforded ethyl 2-(3-methylsulfanylphenyl)-3-(tetrahydropyran-4-yl)propionate: m/z (ES+)=309.2 [M+H]+. Saponification of this ester with LiOH.H2O, by the protocol outlined in Preparation 22, furnished the title compound: m/z (ES+)=561.3 [2M+H]+.

Workup

  1. customdescribed in Preparation 30

Sources & evidence

ORD record
ord-3c493ff69a144bfaa6a4e7a974a89630
Source dataset
uspto-grants-2009_09
Patent number
US07582632B2

Reaction notes

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