1,2-Dichloroethane → N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-(1-naphthylmethyl)glycine methionine methyl ester

HRID 259969Notes

Reaction equation

HRID 259969 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@@H:27]([CH3:30])[CH2:28][CH3:29])[CH2:10][N:11]([CH2:16][C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][CH:18]=1)[CH2:12][C:13]([OH:15])=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH3:46][O:47][C:48](=[O:55])[C@H:49]([CH2:51][CH2:52][S:53][CH3:54])[NH2:50].CCN(CC)CC>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@@H:27]([CH3:30])[CH2:28][CH3:29])[CH2:10][N:11]([CH2:16][C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][CH:18]=1)[CH2:12][C:13]([OH:15])=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:46][O:47][C:48](=[O:55])[C@H:49]([CH2:51][CH2:52][S:53][CH3:54])[NH2:50]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 22861722N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-(1-naphthylmethyl)glycine

Product 1

HCID 67554562N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-(1-naphthylmethyl)glycine methionine methyl esterYield 100.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-(1-naphthylmethyl)glycine (2.29 g, 5.53 mmol), dissolved in DMF (20 mL), was treated with HOBT (0.822 g, 6.08 mmol), EDC (1.17 g, 6.08 mmol), and methionine methyl ester hydrochloride (1.21 g, 6.08 mmol). The pH was adjusted to 7.5 with Et3N (1.7 mL, 12 mmol) and the mixture was stirred at ambient temperature for 24 h. The mixture was concentrated, and the residue was partitioned between EtOAc (50 mL) and saturated NaHCO3 solution (25 mL). The aqueous layer was extracted with EtOAc (1×30 mL). The organic layers were combined, washed with brine (1×25 mL), dried (Na2SO4), filtered, and concentrated to give 3.2 g of crude product which was purified by chromatography (silica gel eluting with 1:3 to 1:2 ethyl acetate in hexane) to give pure product. 1H NMR (CD3OD) δ8.33 (1H, d, J=6 Hz), 7.90 (1H, d, J=6 Hz), 7.82 (1H, d, J=6 Hz), 7.61-7.39 (4H, m), 6.60-6.52 (1H, m), 4.32-4.06 (2H, m), 3.90-3.69 (1H, m), 3.65 (3H, s), 3.27-3.14 (2H, m), 2.93-2.70 (2H, m), 2.19-1.78 (6H, m), 1.63-1.30 (13H, m), 1.19-1.05 (1H, m), 0.95-0.81 (6H, m) ppm.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between EtOAc (50 mL) and saturated NaHCO3 solution (25 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (1×30 mL)
  4. washwashed with brine (1×25 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-b9454d2710924a3ba4883a030043c786
Source dataset
uspto-grants-1996_06
Patent number
US05523456

Reaction notes

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