Triethylamine → (S)-2-{3-(S)-allyl-4-[2-(R)-tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methyl ester

HRID 720163Notes

Reaction equation

HRID 720163 reaction equation
[CH3:1][O:2][C:3](=[O:26])[C@@H:4]([N:16]1[CH2:21][CH2:20][NH:19][C@@H:18]([CH2:22][CH:23]=[CH2:24])[C:17]1=[O:25])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.[C:27]([O:31][C:32]([NH:34][C@H:35]([CH2:39][C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=1)[C:36](O)=[O:37])=[O:33])([CH3:30])([CH3:29])[CH3:28].C(N(CC)CC)C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:26])[C@@H:4]([N:16]1[CH2:21][CH2:20][N:19]([C:36](=[O:37])[C@H:35]([NH:34][C:32]([O:31][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:33])[CH2:39][C:40]2[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=2)[C@@H:18]([CH2:22][CH:23]=[CH2:24])[C:17]1=[O:25])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2734493(2R)-2-(((tert-butoxy)carbonyl)amino)-3-(4-fluorophenyl)propanoic acidHCID 25131150(S,S)-2-(3-allyl-2-oxo-piperazin-1-yl)-3-naphthalen-2-yl-propionic acid methyl ester

Product 1

HCID 25131475(S)-2-{3-(S)-allyl-4-[2-(R)-tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S,S)-2-(3-allyl-2-oxo-piperazin-1-yl)-3-naphthalen-2-yl-propionic acid methyl ester, 5, (500 mg, 1.42 mmol) in CH2Cl2 (5.0 mL) are added 2-(R)-tert-butoxycarbonylamino-3-(4-fluorophenyl)propionic acid (473 mg, 1.67 mmol), benzotriazole-1-yl-oxy-tris-pyrrolidinol-phosphonium hexafluorophosphate (PyBOP) (960 mg, 1.85 mmol) and triethylamine (169 mg, 1.67 mmol). The reaction mixture is stirred for 20 h, quenched with 10% NaHCO3 aqueous solution and extracted with EtOAc. The extract is dried over Na2SO4, filtered and concentrated. The residue is purified over silica gel (hexanes/ethyl acetate, 4:1 to 3:2) to afford 0.745 g (85% yield) of the desired product.

Workup

  1. customquenched with 10% NaHCO3 aqueous solution
  2. extractionextracted with EtOAc
  3. dry with materialThe extract is dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified over silica gel (hexanes/ethyl acetate, 4:1 to 3:2)

Sources & evidence

ORD record
ord-6087cf4ec1994a8fa21ce76021d1f26f
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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