1,2-Dichloroethane → (2R,5R)-methyl 2,5-dibenzyl-6-oxo-6-((R)-2-oxo-1-phenylazepan-3-ylamino)hexanoate

HRID 529454Notes

Reaction equation

HRID 529454 reaction equation
[CH2:1]([C@@H:8]([CH2:12][CH2:13][C@H:14]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:15]([O:17][CH3:18])=[O:16])[C:9]([OH:11])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[NH2:33][C@H:34]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]1=[O:47].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:19]([C@@H:14]([CH2:13][CH2:12][C@H:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:9](=[O:11])[NH:33][C@@H:34]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]1=[O:47])[C:15]([O:17][CH3:18])=[O:16])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 68292211(2R,5R)-2,5-dibenzyl-6-methoxy-6-oxohexanoic acidHCID 86706192(S)-3-amino-1-phenylazepan-2-one trifluoroacetic acid salt

Product 1

HCID 86706191(2R,5R)-methyl 2,5-dibenzyl-6-oxo-6-((R)-2-oxo-1-phenylazepan-3-ylamino)hexanoateYield 70.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a round bottom flask was added (2R,5R)-2,5-dibenzyl-6-methoxy-6-oxohexanoic acid (278 mg, 0.817 mmol), (S)-3-amino-1-phenylazepan-2-one trifluoroacetic acid salt (260 mg, 0.817 mmol), HOBT (163 mg, 1.062 mmol), EDC (204 mg, 1.062 mmol), Hunig's base (317 mg, 2.45 mmol) and DMF (5 mL). The reaction was stirred at rt for 2 days. The reaction mixture was partitioned between EtOAc and water. The organic phase was isolated, washed with aqueous 0.5 N HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl. The organic phase was then dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 30-60% EtOAc/Hex to give (2R,5R)-methyl 2,5-dibenzyl-6-oxo-6-((R)-2-oxo-1-phenylazepan-3-ylamino)hexanoate (305 mg, 0.579 mmol, 70.9% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.38 (t, J=7.7 Hz, 2H), 7.32-7.20 (m, 5H), 7.20-7.06 (m, 8H), 6.75 (d, J=6.2 Hz, 1H), 4.70 (dd, J=10.0, 6.3 Hz, 1H), 3.90 (dd, J=15.3, 11.4 Hz, 1H), 3.67-3.47 (m, 4H), 2.95-2.82 (m, 2H), 2.77-2.57 (m, 3H), 2.43-2.30 (m, 1H), 2.02-1.78 (m, 3H), 1.77-1.39 (m, 5H), 1.35-1.20 (m, 2H).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. customThe organic phase was isolated
  3. washwashed with aqueous 0.5 N HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl
  4. dry with materialThe organic phase was then dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified
  8. washeluting with a gradient of 30-60% EtOAc/Hex

Sources & evidence

ORD record
ord-51cfc8a9994b4634a72cd0f086e0f991
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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