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

HRID 1350302Notes

Reaction equation

HRID 1350302 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[O:16]1[CH2:21][CH2:20][CH:19]([CH:22]=O)[CH2:18][CH2:17]1>>[N+:1]([C:4]1[CH:5]=[C:6]([C:10](=[CH:22][CH:19]2[CH2:20][CH2:21][O:16][CH2:17][CH2:18]2)[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]

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-methylsulfanyl-phenyl)-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-511615dbcd1b4cd98ddf1a11d6282a5e
Source dataset
uspto-grants-2007_05
Patent number
US07214681B2

Reaction notes

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