1,2-Dichloroethane → HCID 58649548, compound

HRID 1830165Notes

Reaction equation

HRID 1830165 reaction equation
[N:1]1([C:7](=[O:24])[CH2:8][CH:9]([CH2:13][S:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:16])=[O:15])[C:10]([OH:12])=O)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:39][C@@H:40]([CH2:52][CH3:53])[CH:41]([C:43]1[O:44][C:45]2[CH:51]=[CH:50][CH:49]=[CH:48][C:46]=2[N:47]=1)[OH:42].CN1CCOCC1.[O-]S([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.C([O-])(O)=O.[Na+]>[O:44]1[C:45]2[CH:51]=[CH:50][CH:49]=[CH:48][C:46]=2[N:47]=[C:43]1[C:41]([C@@H:40]([NH:39][C:10](=[O:12])[CH:9]([CH2:13][S:14]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:16])=[O:15])[CH2:8][C:7]([N:1]1[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1)=[O:24])[CH2:52][CH3:53])=[O:42]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 24437Sodium SulfiteHCID 757711-HydroxybenzotriazoleHCID 11665617HCID 11665617, compoundHCID 220539874-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid

Product 1

HCID 58649548HCID 58649548, compoundYield 82.9%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture comprised of 4-Morpholin-4-yl-4-oxo-2-(benzyl-sulfonylmethyl)-butyric acid (300 mg, 0.84 mmol), EDC (250 mg, 1.3 mmol), HOBt (250 mg, 1.6 mmol) and (2S)-2-amino-1-benzooxazol-2-yl-butan-1-ol (250 mg, 1.2 mmol) was treated with dichloromethyl (4 mL) followed by 4-methylmorpholine (0.5 mL). The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (150 mL), the solution was washed with 1N aqueous HCl, water, saturated aqueous NaHCO3 solution and brine, dried with magnesium sulfate and evaporated under vacuum. The crude product was dissolved in dry dichloromethyl (10 mL) and 1,1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane) (500 mg, 1.2 mmol) was added. After stirring at ambient temperature for 1 hour, the mixture was diluted with ethyl acetate (150 mL) and treated with 0.26M Na2SO3 solution in saturated aqueous NaHCO3. The organic phase was washed with saturated aqueous NaHCO3 and brine, dried with magnesium sulfate and evaporated to yield N-[(S)-1-(1-Benzooxazol-2-yl-methanoyl)-propyl]-4-morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyramide (377 mg) as mixture of diastereomers. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate ratio of 1:2 to 1:4); 1H NMR: (DMSO), 8.85 (d, J=6.2 Hz), 8.77 (d, J=6.2 Hz), 1H],, 8.00 (d, J=7.7 Hz), 7.99 (d, J=7.7 Hz), 1H],, 7.90 (d, J=8.2 Hz), 7.89 (d, J=8.2 Hz), 1H], 7.64 (t, J=7.9 Hz, 1H), 7.54 (t, J=7.4 Hz, 1H), 7.42–7.34 (m, 5H), 5.25–5.12 (m, 1H), 4.55–4.38 (m, 2H), 3.60–3.28 (m, 10H), 3.12–3.02 (m, 1H), 2.64–2.50 (m, 2H), 2.08–1.91 (m, 1H), 1.82–1.65 (m, 1H), 0.98 (t, J=7.4 Hz, 3H); MS: (M++1) 542;

Workup

  1. additionwas treated with dichloromethyl (4 mL)
  2. washAfter dilution with ethyl acetate (150 mL), the solution was washed with 1N aqueous HCl, water, saturated aqueous NaHCO3 solution and brine
  3. dry with materialdried with magnesium sulfate
  4. customevaporated under vacuum
  5. dissolutionThe crude product was dissolved in dry dichloromethyl (10 mL)
  6. stirringAfter stirring at ambient temperature for 1 hour
  7. washThe organic phase was washed with saturated aqueous NaHCO3 and brine
  8. dry with materialdried with magnesium sulfate
  9. customevaporated

Sources & evidence

ORD record
ord-fae45576176e40c4a630eccb4463d3f6
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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