Dimethylformamide → 3-(4'-Bromobiphenyl-4-ylmethylsulfanyl)-2-tert-butoxycarbonylamino-propionic Acid Methyl Ester

HRID 1782658Notes

Reaction equation

HRID 1782658 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14]Br)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:16][O:17][C:18](=[O:30])[C@H:19]([CH2:28][SH:29])[NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>O>[CH3:16][O:17][C:18](=[O:30])[CH:19]([NH:20][C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:28][S:29][CH2:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=2)=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 10977409N-(tert-Butoxycarbonyl)-L-cysteine methyl esterHCID 201373444-Bromo-4'-(bromomethyl)-1,1'-biphenyl

Product 1

HCID 688180613-(4'-Bromobiphenyl-4-ylmethylsulfanyl)-2-tert-butoxycarbonylamino-propionic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4′-Bromo-4-bromomethyl-biphenyl, 9.1 g (27.9 mmol), N-(tert-Butoxy-carbonyl)-L-cysteine methyl ester, 5.74 mL (27.9 mmol), cesium carbonate, 18.2 g (55.8 mmol), and 100 mL of N,N-dimethylformamide was stirred at room temperature for 4 h. The mixture was diluted with 200 mL of water and extracted with 2×200 mL of ethyl acetate. The organic layer was washed with 2×200 mL portions of aq. LiCl, sat. aq. NaHCO3, sat. aq. NaCl, and dried (MgSO4). After the solution was concentrated, the residue was purified through a short plug of silica gel (eluted with 20% EtOAc-Heptane) to afford the desired product in 8.8 g (66%) as a white solid. 1H NMR (CDCl3) 7.55 (d, 2H, J=9.3 Hz), 7.50 (d, 2H, J=9.0 Hz), 7.43 (d, 2H, J=9.3 Hz), 7.37 (d, 2H, J=9.0 Hz), 5.31 (d, 1H, J=9.0 Hz), 4.62-4.51 (m, 1H), 3.76 (s, 5H), 2.93 (dd, 1H, 15.7, 5.7 Hz), 2.84 (dd, 1H, 15.7, 6.3 Hz), 1.47 (s, 9H).

Workup

  1. extractionextracted with 2×200 mL of ethyl acetate
  2. washThe organic layer was washed with 2×200 mL portions of aq. LiCl, sat. aq. NaHCO3, sat. aq. NaCl
  3. dry with materialdried (MgSO4)
  4. concentrationAfter the solution was concentrated
  5. customthe residue was purified through a short plug of silica gel (eluted with 20% EtOAc-Heptane)

Sources & evidence

ORD record
ord-2a5c271ada4a460a91ac4613c6188126
Source dataset
uspto-grants-2009_03
Patent number
US07498356B2

Reaction notes

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