N-Methyl dicyclohexylamine → HCID 70983307, compound

HRID 403353Notes

Reaction equation

HRID 403353 reaction equation
Br[C:2]1[N:3]=[CH:4][S:5][C:6]=1[C@@H:7]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:8]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[F:24])[CH2:9][CH2:10]/[CH:11]=[CH:12]/[C:13]([O:15][CH3:16])=[O:14].CN(C1CCCCC1)C1CCCCC1>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:29]([O:28][C:26]([NH:25][C@@H:7]1[C:6]2[S:5][CH:4]=[N:3][C:2]=2/[C:11](=[CH:12]/[C:13]([O:15][CH3:16])=[O:14])/[CH2:10][CH2:9][C@H:8]1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[F:24])=[O:27])([CH3:32])([CH3:31])[CH3:30]

Participants

5

Reactant 2

HCID 24210N-Methyl dicyclohexylamineHCID 70983668HCID 70983668, compound

Product 1

HCID 70983307HCID 70983307, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (6S,7S,E)-methyl 7-(4-bromothiazol-5-yl)-7-(tert-butoxycarbonylamino)-6-(2,3-difluorophenyl)hept-2-enoate (0.217 g, 0.409 mmol), bis(tri-t-butylphosphine)palladium (0) (0.021 g, 0.041 mmol) and methyl dicyclohexylamine (0.096 mL, 0.450 mmol) in dioxane (10 mL) (degassed with nitrogen) was heated at 140° C. under microwave radiation for 1 h under nitrogen. The solvent was removed under vacuum and the product was purified by flash chromatography eluting with ethyl acetate in hexane from 0 to 45% to afford the desired product (53.4 mg, 29%), (M+H=451.20), as well as the isomerized product (double bond moved into the ring) (108.8 mg, 59%) as the major component.

Workup

  1. customThe solvent was removed under vacuum
  2. customthe product was purified by flash chromatography
  3. washeluting with ethyl acetate in hexane from 0 to 45%

Sources & evidence

ORD record
ord-14eafc66ee774d5a8b237edb87c3653c
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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