1,2-Dichloroethane → (RS)-N-(4-cyano-benzyl)-2-(2,6-difluoro-3-hydroxy-phenyl)-2-ethoxy-acetamide

HRID 1247386Notes

Reaction equation

[F:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([F:9])[C:3]=1[CH:10]([O:14][CH2:15][CH3:16])[C:11]([OH:13])=O.Cl.[NH2:18][CH2:19][C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1.ON1C2C=CC=CC=2N=N1.C(Cl)CCl>CN(C=O)C.C(N(CC)CC)C>[C:19]([C:20]1[CH:27]=[CH:26][C:23]([CH2:24][NH:25][C:11](=[O:13])[CH:10]([C:3]2[C:4]([F:9])=[CH:5][CH:6]=[C:7]([OH:8])[C:2]=2[F:1])[O:14][CH2:15][CH3:16])=[CH:22][CH:21]=1)#[N:18]

Participants

Conditions

Temperature: 0 °C

Procedure

To an ice cooled mixture under Ar of (RS)-(2,6-difluoro-3-hydroxy-phenyl)-ethoxy-acetic acid, 4-aminomethyl-benzonitrile hydrochloride (10.6 g) and 1-hydroxybenzotriazole (9.8 g) in DMF (140 ml) was added EDC (13.9 g) and triethylamine (55 ml). The mixture was stirred 2.5 h at 0° C. and 2 d at rt. The solvent was evaporated and H2O (250 ml) was added. The product was extracted with AcOEt (2×200 ml). The organic layers were washed with 5% NaHCO3 aq. sol. (100 ml), brine 100 ml). After drying (Na2SO4) the solvent was evaporated. CC (AcOEt/Hept 2:3) afforded 7.66 g (49%) of (RS)-N-(4-cyano-benzyl)-2-(2,6-difluoro-3-hydroxy-phenyl)-2-ethoxy-acetamide. White solid. MS 364.1 ([M+NH4]+).

Workup

customThe solvent was evaporated
additionH2O (250 ml) was added
extractionThe product was extracted with AcOEt (2×200 ml)
washThe organic layers were washed with 5% NaHCO3 aq. sol. (100 ml), brine 100 ml)
dry with materialAfter drying (Na2SO4) the solvent
customwas evaporated

Sources & evidence

ORD record: ord-b6daa188619a46f19b7453fd9c40ce6c
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07129238B2

Reaction notes

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