Triethylamine → HCID 58005157, compound

HRID 1879264Notes

Reaction equation

HRID 1879264 reaction equation
[CH:1]([B-](F)(F)F)=[CH2:2].[K+].CCN(CC)CC.Br[C:16]1[CH:17]=[C:18]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][O:29][C@H:30]3[CH2:34][N:33]([C:35](=[O:51])[C@@H:36]([NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH:37]4[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]4)[C@H:32]([C:52]([O:54][CH3:55])=[O:53])[CH2:31]3)[CH:23]=2)[CH:19]=[CH:20][CH:21]=1.CCOC(C)=O>CCO.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:47]([O:46][C:44]([NH:43][C@@H:36]([CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1)[C:35]([N:33]1[CH2:34][C@H:30]([O:29][CH2:28][C:24]2[CH:23]=[C:22]([C:18]3[CH:19]=[CH:20][CH:21]=[C:16]([CH:1]=[CH2:2])[CH:17]=3)[CH:27]=[CH:26][CH:25]=2)[CH2:31][C@H:32]1[C:52]([O:54][CH3:55])=[O:53])=[O:51])=[O:45])([CH3:50])([CH3:48])[CH3:49]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 23679353Potassium vinyltrifluoroborateHCID 58005171HCID 58005171, compound

Product 1

HCID 58005157HCID 58005157, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Potassium vinyltrifluoroborate (2.0 eq.), Et3N (2.0 eq.) and PdCl2(dppf)-DCM adduct (0.05 eq.) were sequentially added to a 0.12 M solution of methyl (4R)-4-[(3′-bromobiphenyl-3-yl)methoxy]-1-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl}-L-prolinate 106 in EtOH. The reaction mixture was stirred with heating at reflux for 3 h then it was cooled down to RT and diluted with H2O:EtOAc. The phases were separated and the organic layer was washed with brine, dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by flash chromatography (SiO2, PE:EtOAc=8:2) to afford the title compound 107 (72%) as a foam. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 7.75 (s, 1H), 7.71-7.61 (m, 2H), 7.59 (d, J 7.3, 1H), 7.56-4.43 (m, 3H), 7.39 (d, J 7.3, 1H), 6.94 (d, J 8.6, 1H), 6.86 (dd, J 17.7, 10.9, 1H), 5.98 (d, J 17.7, 1H), 5.36 (d, J 10.9, 1H), 4.66 (d, J 11.7, 1H), 4.58 (d, J 11.7, 1H), 4.36 (t, J 8.6, 1H), 4.32 (bs, 1H), 4.19 (d, J 10.9, 1H), 4.15-4.07 (m, 1H), 3.73-3.66 (m, 1H), 3.65 (s, 3H), 2.46-2.35 (m, 1H), 2.07-1.98 (m, 1H), 1.82-1.57 (m, 6H), 1.42-1.36 (m, 1H), 1.34 (s, 9H), 1.20-1.12 (m, 2H), 1.07-0.94 (m, 2H). MS (ES+) m/z 577 (M+H)+

Workup

  1. temperaturewith heating
  2. temperatureat reflux for 3 h
  3. customThe phases were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated under reduced pressure
  7. customThe residue was purified by flash chromatography (SiO2, PE:EtOAc=8:2)

Sources & evidence

ORD record
ord-d29e013df77f4c2c940715e8a4efefc4
Source dataset
uspto-grants-2012_11
Patent number
US08314062B2

Reaction notes

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