Water → HCID 15454949, compound

HRID 2287517Notes

Reaction equation

HRID 2287517 reaction equation
O.[CH2:2]([O:9][C:10]([N:12]1[C@H:16]([CH3:17])[C@H:15]([CH2:18][OH:19])[C@H:14]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@@H:13]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CCN(CC)CC>CS(C)=O>[CH2:2]([O:9][C:10]([N:12]1[C@H:16]([CH3:17])[C@H:15]([CH:18]=[O:19])[C@H:14]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@@H:13]1[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 962Water2×HCID 8471TriethylamineHCID 15454945HCID 15454945, compound

Product 1

HCID 15454949HCID 15454949, compoundYield 141.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred and water-cooled solution of (2S*,3S*,4R*,5R*)-1-benzyloxycarbonyl-3-[N-(t-butoxycarbonyl)amino]-4-hydroxymethyl-5-methyl-2-phenylpyrrolidine (2.60 g, 5.90 mmol) and Et3N (5.70 ml, d0.726, 40.9 mmol) in DMSO (dried over molecular sieves 4, 36 ml) was added sulfer trioxide pyridine complex (SO3Py, Wako, 5.42 g, 34.1 mmol) portionwise. Just after the addition the water bath was removed, and the stirring was continued at room temperature for 1.5 hours. The reaction mixture was poured into a mixture of ice and water (80 ml). The mixture was extracted with CH2Cl2 (30 ml×5). The combined CH2Cl2 extracts were washed with 10% citric acid aq. solution (30 ml×4) until the aqueous washing reached the acidity of citric acid (pH ca.3), H2O (30 ml×1), sat. NaHCO3 aq. solution (40 ml×1), and sat. NaCl aq. solution (×1), dried (MgSO4), and concentrated in vacuo to give crude title compound (3.66 g, quant.) as a pale yellow viscous oil; while the yield was overestimated owing to contamination with the solvent employed, this crude product solidified on standing in a refrigerator: IRmax (film): 3400(m, shoulder), 3350(m), 2720(w), 1710(vs), 1690(vs, shoulder), 1605(w), 1585(w), 1520(s), 1500(s), 1165(s), 770(m), 730(s), 700(s) cm-1 ; 1H-NMR δ: 9.65(d, J=3.7 Hz, 1H), 7.40-7.10(m, 9H), 7.05(br.s, 1H), 5.27(d, J=8.5 Hz, 1H), 5.06(br.s, 2H), 4.78-4.57(m, 1H), 4.24(dq, J=9.5, 6.1 Hz, 1H), 4.05(br.d, J=9.2 Hz, 1H), 2.77-2.50(m, 1H), 1.61(d, J=6.1 Hz, 1H), 1.37(s, 9H) ppm. This was employed in the next step without further purification.

Workup

  1. additionwas added sulfer trioxide pyridine complex (SO3Py, Wako, 5.42 g, 34.1 mmol) portionwise
  2. customwas removed
  3. additionThe reaction mixture was poured into a mixture of ice and water (80 ml)
  4. extractionThe mixture was extracted with CH2Cl2 (30 ml×5)
  5. washThe combined CH2Cl2 extracts were washed with 10% citric acid aq. solution (30 ml×4) until the
  6. washaqueous washing
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e670025915d1493b8e83c054dcd990fb
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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