Dimethylformamide → (2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

HRID 1021057Notes

Reaction equation

HRID 1021057 reaction equation
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C@@H:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1.CN(C)C=O.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:40](I)[CH3:41]>O>[CH2:40]([O:12][C:11](=[O:13])[C@H:10]([CH3:14])[CH2:9][C@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:7][C:4]1[CH:3]=[CH:2][C:1]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:6][CH:5]=1)[CH3:41].[C:1]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:9][C@@H:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6340IodoethaneHCID 10796Cesium carbonateHCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

Product 2

HCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acidHCID 58027501(2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

50 g of (2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid (3-a, R1=BOC, R2=R3=H) is added to dimethylformamide (80 ml). Cesium carbonate (69 g) is then added. Ethyl iodide (13.6 g) is then added and the mixture is stirred overnight at room temperature. Water (200 ml) is added to the mixture and the mixture is then extracted with isopropyl acetate (2×200 ml). The combined organic phases are washed with brine, dried (MgSO4) and concentrated in vacuo to give (2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid ethyl ester (3-a, R1=BOC, R2=H, R3=Et) (56 g). 1H NMR (DMSO): 1.12 (3H), 1.19 (3H), 1.36 (9H), 1.53 (1H), 1.84 (1H), 2.55 (1H), 2.75 (2H), 3.74 (1H), 4.05 (2H), 6.04 (1H), 7.23 (2H), 7.30 (1H), 7.41 (2H), 7.50 (2H), 7.57 (2H). m/z (ES+): 412 ([MH]+, 100%), 356 (63), 312 (73).

Workup

  1. extractionthe mixture is then extracted with isopropyl acetate (2×200 ml)
  2. washThe combined organic phases are washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0b79e8309dea4d72b486d480ac144b73
Source dataset
uspto-grants-2014_05
Patent number
US08716495B2

Reaction notes

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