1,2-Dichloroethane → Morpholine-4-carboxylic acid[1-(4-oxo-tetrahydro-furan-3-ylcarbamoyl)-2-phenylmethanesulfonyl-ethyl]-amide

HRID 460419Notes

Reaction equation

HRID 460419 reaction equation
[N:1]1([C:7]([NH:9][CH:10]([CH2:14][S:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:17])=[O:16])[C:11](O)=[O:12])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[NH2:25][CH:26]1[CH2:30][O:29][CH2:28][CH:27]1[OH:31].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>CN(C=O)C>[O:31]=[C:27]1[CH2:28][O:29][CH2:30][CH:26]1[NH:25][C:11]([CH:10]([NH:9][C:7]([N:1]1[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1)=[O:8])[CH2:14][S:15]([CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)(=[O:17])=[O:16])=[O:12]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 159087TriacetoxyperiodinaneHCID 104868094-Aminotetrahydrofuran-3-olHCID 112797342-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid

Product 1

HCID 10114094Morpholine-4-carboxylic acid[1-(4-oxo-tetrahydro-furan-3-ylcarbamoyl)-2-phenylmethanesulfonyl-ethyl]-amideYield 7.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid (100 mg, 0.28 mmol), 4-aminotetrahydrofuran-3-ol (100 mg, 0.96 mmol), EDC (200 mg, 1.04 mmol), and HOBt (200 mg, 1.28 mmol) were combined. DMF (2 mL) was added and then 4-methylmorpholine (0.2 mL). The mixture was stirred at ambient temperature for 2 h. After dilution with ethyl acetate (100 mL) the solution was washed with 1N aqu. HCl (30 mL), sat. aqu. NaHCO3 (30 mL) and brine (30 mL), dried with MgSO4 and evaporated under vacuum. The crude product was dissolved in dichloromethane (10 mL). Dess-Martin periodinane (300 mg, 0.71 mmol) was added, and the reaction mixture was stirred at ambient temperature for 1 h. After dilution with ethyl acetate (100 mL), the solution was washed with 0.26M Na2S2O3 in sat. aqu. NaHCO3 (30 mL), sat. aqu. NaHCO3 and brine, dried with MgSO4, and evaporated under vacuum. Purification by flash-chromatography on silica gel (ethyl acetate) gave morpholine-4-carboxylic acid [1-(4-oxo-tetrahydro-furan-3-ylcarbamoyl)-2-phenylmethanesulfonyl-ethyl]-amide (8.6 mg, 0.020 mmol) as a colorless glass. Mixture of diastereomers: 1H NMR: (DMSO) [8.42 (d, J=6.8 Hz), 7.15 (d, J=7.2 Hz), 1H], 7.40–7.32 (m, 5H), [7.06 (d, J=8 Hz), 7.05 (d, J=8 Hz), 1H], 4.78–4.68 (m, 1H), 4.49 (s), 4.48 (s), 2H], 4.32–3.75 (m, 5H), 3.60–3.23 (m, 10H). MS: (M+H)+ 440.

Workup

  1. washAfter dilution with ethyl acetate (100 mL) the solution was washed with 1N aqu
  2. dry with materialNaHCO3 (30 mL) and brine (30 mL), dried with MgSO4
  3. customevaporated under vacuum
  4. dissolutionThe crude product was dissolved in dichloromethane (10 mL)
  5. stirringthe reaction mixture was stirred at ambient temperature for 1 h
  6. washAfter dilution with ethyl acetate (100 mL), the solution was washed with 0.26M Na2S2O3 in sat. aqu
  7. dry with materialNaHCO3 and brine, dried with MgSO4
  8. customevaporated under vacuum
  9. customPurification by flash-chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-f4d7fb47ba13425aa90919bef789630b
Source dataset
uspto-grants-2007_03
Patent number
US07196099B2

Reaction notes

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