Benzoic Acid → HCID 86602359, compound

HRID 2111870Notes

Reaction equation

HRID 2111870 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]=O)=[CH:15][CH:14]=2)=[CH:8][CH:7]=1.C(O)(=O)C1C=CC=CC=1.N1CCCCC1.[S:45]1[CH2:49][C:48](=[O:50])[NH:47][C:46]1=[O:51]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.CO.O>[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:21][C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[C:49]3[S:45][C:46](=[O:51])[NH:47][C:48]3=[O:50])=[CH:15][CH:14]=2)=[CH:8][CH:7]=1

Participants

8

Reactant 4

HCID 243Benzoic AcidHCID 5437ThiazolidinedioneHCID 8082PiperidineHCID 86602358HCID 86602358, compound

Product 1

HCID 86602359HCID 86602359, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 21584188Chloroform methanolSolvent

Procedure

Dissolve (S)-2-tert-butoxycarbonylamino-3-(4-(4-formylphenoxy)phenyl)-propanoic acid methyl ester (3.05 Kg, 7.64 moles) in toluene (18 L). Add benzoic acid (144.9 g), piperidine (87.6 g) and 2,4-thiazolidinedione (1.11 Kg, 20.5) sequentially. Remove water azeotropically for 6 h. Check completion of the reaction by TLC (SiO2 gel, CHCl3-MeOH, 19:1). Distil off half of the solvent and cool down to room temperature, washed with 5% sodium bicarbonate solution, water, brine and dried over anhydrous sodium sulfate. Yield 3.80 Kg, 99.9%, chiral purity 100% ee. 1HNMR (300 MHz, CD3OD): 7.75 (s, 1H), 7.52 (d, J=9.0 Hz, 2H) 7.26 (d, J=8.4 Hz, 2H), 7.26 (d, J=8.4 Hz, 2H), 7.03 (d, J=9.0 Hz, 2H), 6.95 (d, J=9.0 Hz, 2H), 4.38 (m, 1H), 3.71 (S, 3H), 3.12 (dd, J=5.4 and 13.5 Hz, 1H), 2.85 (dd, J=9.3 and 13.5 Hz, 1H), 1.30 (s, 9H).

Workup

  1. customDistil off half of the solvent
  2. washwashed with 5% sodium bicarbonate solution, water, brine
  3. dry with materialdried over anhydrous sodium sulfate

Sources & evidence

ORD record
ord-46a9461433e3459cb35db04f0b82e5a7
Source dataset
uspto-grants-2009_04
Patent number
US07521465B2

Reaction notes

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