Dimethylformamide → (R)-3-[4-(4-Benzoyl-phenoxy)-phenyl]-2-tert-butoxycarbonylamino-propionic acid methyl ester

HRID 1669498Notes

Reaction equation

HRID 1669498 reaction equation
CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[CH3:12][O:13][C:14](=[O:32])[C@@H:15]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)[NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].F[C:34]1[CH:47]=[CH:46][C:37]([C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:39])=[CH:36][CH:35]=1>O>[CH3:12][O:13][C:14](=[O:32])[C@H:15]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:18])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][C:43]2[CH:44]=[CH:45][C:40]([C:38](=[O:39])[C:37]3[CH:46]=[CH:47][CH:34]=[CH:35][CH:36]=3)=[CH:41][CH:42]=2)=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 676634-FluorobenzophenoneHCID 7016055Boc-D-Tyr-OMe

Product 1

HCID 67351929(R)-3-[4-(4-Benzoyl-phenoxy)-phenyl]-2-tert-butoxycarbonylamino-propionic acid methyl esterYield 24%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of N,N-Dimethylformamide (DMF) (3.16 mL) and potassium carbonate (0.222 g, 1.605 mmol) was added Boc-D-Tyrosine-Methyl ester (0.158 g, 0.535 mmol) and 4-Fluorobenzophenone (0.160 g, 0.802 mmol) at 100° C. under an atmosphere of nitrogen for 42 hours. The mixture was poured into 30 mL water solution and extracted with ethyl acetate (EtOAc) (4×10 mL). The combined organic layers were washed with brine (40 mL) and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo to obtain the crude mixture, which was purified by of silica gel flash chromatography, using EtOAc/hexane (gradient system), to obtain the product (0.060 g, 24%): 1H NMR (400 MHz, CDCL3): δ 1.42 (s, 9H), 2.99-3.17 (m, 2H), 3.71-3.74 (m, 3H), 4.53-4.61 (m, 1H), 4.96-5.16 (m, 1H), 6.75 (d, 1H, J=8.4 Hz), 6.97-7.03 (m, 4H), 7.16 (d, 2H, J=8.4 Hz), 7.46-7.50 (m, 2H), 7.56-7.58 (m, 1H), 7.77-7.83 (m, 3H).

Workup

  1. extractionextracted with ethyl acetate (EtOAc) (4×10 mL)
  2. washThe combined organic layers were washed with brine (40 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationThe organic layer was concentrated in vacuo
  5. customto obtain the crude mixture, which
  6. customwas purified by of silica gel flash chromatography

Sources & evidence

ORD record
ord-4f9f6772dec54df5a2f6747c8b71c3a7
Source dataset
uspto-grants-2011_08
Patent number
US07989480B2

Reaction notes

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