1,2-Dichloroethane → HCID 178456079, compound

HRID 2212242Notes

Reaction equation

HRID 2212242 reaction equation
[CH:1]1([CH2:7][C@H:8]([NH:12][C:13]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[S:15](=[O:23])(=[O:22])[N:14]=2)[C:9](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:38][C@@H:39]([CH2:51][CH3:52])[CH:40]([C:42]1[O:43][C:44]2[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=2[N:46]=1)[OH:41].CN1CCOCC1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(OCC)(=O)C.C([O-])(O)=O.[Na+].ClCCl>[O:43]1[C:44]2[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=2[N:46]=[C:42]1[C:40]([C@@H:39]([NH:38][C:9](=[O:10])[C@@H:8]([NH:12][C:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[S:15](=[O:23])(=[O:22])[N:14]=1)[CH2:7][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[CH2:51][CH3:52])=[O:41]

Participants

11

Reactant 7

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 24477Sodium ThiosulfateHCID 757711-HydroxybenzotriazoleHCID 159087TriacetoxyperiodinaneHCID 11665617HCID 11665617, compoundHCID 178525806HCID 178525806, compound

Product 1

HCID 178456079HCID 178456079, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

(S)-3-Cyclohexyl-2-(1,1-dioxo-benzo[d]isothiazol-3-ylamino)-propionic acid (150 mg, 0.45 mmol) was combined with EDC (250 mg, 1.3 mmol), HOBt (250 mg, 1.6 mmol), and (2S)-2-amino-1-benzoxazol-2-ylbutan-1-ol (250 mg, 1.2 mmol). Dichloromethane (4 mL) was added and then 4-methylmorpholine (0.5 mL). The reaction mixture was stirred at ambient temperature for 2 h. After dilution with ethyl acetate (150 mL), the solution was washed with 1N aqueous HCl, water, saturated aqueous NaHCO3 solution and brine, dried with MgSO4 and evaporated under vacuum. The crude product was dissolved in dry dichloromethane (10 mL) and Dess-Martin Periodinane (500 mg, 1.2 mmol) was added. After stirring at ambient temperature for 1 h, the reaction mixture was diluted with ethyl acetate (150 mL) and treated with 0.26M Na2S2O3 solution in saturated aqueous NaHCO3. The organic phase was washed with saturated aqueous NaHCO3 and brine, dried with MgSO4 and evaporated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate 2:1) to yield the title compound (120 mg).

Workup

  1. washAfter dilution with ethyl acetate (150 mL), the solution was washed with 1N aqueous HCl, water, saturated aqueous NaHCO3 solution and brine
  2. dry with materialdried with MgSO4
  3. customevaporated under vacuum
  4. dissolutionThe crude product was dissolved in dry dichloromethane (10 mL)
  5. stirringAfter stirring at ambient temperature for 1 h
  6. washThe organic phase was washed with saturated aqueous NaHCO3 and brine
  7. dry with materialdried with MgSO4
  8. customevaporated
  9. customThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-81d2ac56ec434f578a9873a039694c9d
Source dataset
uspto-grants-2006_09
Patent number
US07101880B2

Reaction notes

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