3-Bromopentane → (RS)-N-(4-cyano-benzyl)-2-ethoxy-2-[3-(1-ethyl-propoxy)-2,6-difluoro-phenyl]-acetamide

HRID 1247387Notes

Reaction equation

[C:1]([C:3]1[CH:25]=[CH:24][C:6]([CH2:7][NH:8][C:9](=[O:23])[CH:10]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[C:16]([OH:21])[C:15]=2[F:22])[O:11][CH2:12][CH3:13])=[CH:5][CH:4]=1)#[N:2].Br[CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9](=[O:23])[CH:10]([O:11][CH2:12][CH3:13])[C:14]2[C:19]([F:20])=[CH:18][CH:17]=[C:16]([O:21][CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29])[C:15]=2[F:22])=[CH:24][CH:25]=1)#[N:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution under Ar of (RS)-N-(4-cyano-benzyl)-2-(2,6-difluoro-3-hydroxy-phenyl)-2-ethoxy-acetamide (200 mg) in DMF (10 ml) was added CSCO3 (226 mg) and 3-bromopentane (105 mg). The solution was stirred over night at 80° C. The solvent was evaporated and the residue was taken up in H2O (50 ml). The product was extracted with AcOEt (2×100 ml). The organic layers were washed with H2O (2×50 ml) and dried (NaaSO4) and the solvent was evaporated. CC (AcOEt/Hept 2:3 to AcOEt) afforded 190 mg (79%) of (RS)-N-(4-cyano-benzyl)-2-ethoxy-2-[3-(1-ethyl-propoxy)-2,6-difluoro-phenyl]-acetamide. This material was converted to (RS)-N-(4-carbamimidoyl-benzyl)-2-ethoxy-2-[3-(1-ethyl-propoxy)-2,6-difluoro-phenyl]-acetamide acetate by the sequence of procedures G and H. Off-white solid. MS 434.4 ([M+H]+).

Workup

customThe solvent was evaporated
extractionThe product was extracted with AcOEt (2×100 ml)
washThe organic layers were washed with H2O (2×50 ml)
customdried (NaaSO4)
customthe solvent was evaporated

Sources & evidence

ORD record: ord-258d060bc71f4caa8e75ceeab8ba61d8
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07129238B2

Reaction notes

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