Ethyl 4-nitrophenylacetate → HCID 21094180, compound

HRID 1350299Notes

Reaction equation

HRID 1350299 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:6][CH:5]=1)([O-:3])=[O:2].I[CH2:17][CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH:10]([CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

3

Reactant 2

HCID 79517Ethyl 4-nitrophenylacetateHCID 27955074-(Iodomethyl)oxane

Product 1

HCID 21094180HCID 21094180, compound

Procedure

Ethyl (4-nitrophenyl)acetate (25.0 g, 119.5 mmol) was alkylated with 4-iodomethyltetrahydropyran (32.4 g, 143.4 mmol), according to the protocol described in Preparation 41, to give ethyl 2-(4-nitrophenyl)-3-(tetrahydropyran-4-yl)propionate: δH (CDCl3): 1.21 (3H, t), 1.25–1.45 (3H, m), 1.55–1.65 (2H, m), 1.70–1.80 (1H, m), 2.05–2.15 (1H, m), 3.25–3.35 (2H, m), 3.79 (1H, t), 3.90–3.95 (2H, m), 4.10–4.20 (2H, m), 7.49 (2H, d), 8.19 (2H, d). The nitro group of this compound (6.55 g, 18.1 mmol) was reduced utilising the procedure described in EXAMPLE 145 to give ethyl 2-(4-aminophenyl)-3-(tetrahydropyran-4-yl)propionate: m/z (ES+)=278.2 [M+H]+. This compound (30.5 g, 110 mmol) was transformed into ethyl 2-(4-chlorosulfonylphenyl)-3-(tetrahydropyran-4-yl)propionate employing the protocol described in Preparation 59. A solution of this sulfonyl chloride (33.6 g, 93.2 mmol) in anhydrous THF (100 mL) was added over 30 min at 0° C. to EtNH2 (116.5 mL of a 2.0 M solution in THF, 233.0 mmol). The mixture was warmed up to 20° C., before being stirred for 16 h. The suspension was filtered through a Celite pad, which was washed with THF (3×50 mL). The combined THF solutions were concentrated to furnish crude ethyl 2-(4-ethylsulfamoylphenyl)-3-(tetrahydropyran-4-yl)propionate: m/z (ES+)=370.2 [M+H]+. Hydrolysis of this ester (33.7 g, 91.2 mmol), utilising the procedure outlined in Preparation 41, followed by purification via RP—HPLC afforded the title compound: m/z (ES+)=342.2 [M+H]+.

Workup

  1. customdescribed in Preparation 41

Sources & evidence

ORD record
ord-cb105ecc323e44f8be6ff15122c9fdd7
Source dataset
uspto-grants-2007_05
Patent number
US07214681B2

Reaction notes

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