Methyl iodide → (R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acid

HRID 588324Notes

Reaction equation

HRID 588324 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:10](=[CH2:14])[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1.[C:29](=O)([O-])[O-].CI.C(OC(C)C)(=O)C>O.CN(C)C=O>[CH3:29][O:12][C:11](=[O:13])[C:10](=[CH2:14])[CH2:9][C@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[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.[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])([CH3:21])[CH3:20])=[O:17])[CH2:9][C:10](=[CH2:14])[C:11]([OH:13])=[O:12])=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 7915Isopropyl AcetateHCID 19660Carbonate IonHCID 46193439(R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acid2×

Product 2

HCID 46193439(R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acidHCID 66958027(R)-5-Biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

30 g (R)-5-Biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acid (2-a, R1=Boc, R2=H, R3=CO2H), prepared according to Example 33 is added to 38.4 g caseium carbonate. Dimethylformamide (50 ml) is then added. Methyl iodide (8.26 ml) is then added and the mixture is stirred for 16 h at room temperature. Water (1200 ml) and isopropyl acetate (120 ml) are added. The phases are separated. The aqueous phase is washed with isopropyl acetate (2×120 ml). The combined organic phases are washed with 20% aqueous sodium chloride solution (180 ml) and then dried (MgSO4). The mixture is concentrated under reduced pressure to afford (R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acid methyl ester (2-a, R1=Boc, R2=H, R3=CO2Me). 1H NMR (CDCl3): 1.40 (9H), 2.38 (1H), 2.61 (1H), 2.86 (1H), 2.91 (1H), 3.78 (3H), 4.07 (1H), 4.52 (1H), 5.64 (1H), 6.25 (1H), 7.29 (2H), 7.35 (1H), 7.45 (2H), 7.55 (2H), 7.59 (2H).

Workup

  1. customThe phases are separated
  2. washThe aqueous phase is washed with isopropyl acetate (2×120 ml)
  3. washThe combined organic phases are washed with 20% aqueous sodium chloride solution (180 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationThe mixture is concentrated under reduced pressure

Sources & evidence

ORD record
ord-47dca98518c94071866f81ac411dca01
Source dataset
uspto-grants-2016_01
Patent number
US09227934B2

Reaction notes

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