HCID 131719838, compound → HCID 53921777, compound

HRID 1450204Notes

Reaction equation

HRID 1450204 reaction equation
[O:1]([CH2:8][C:9]([NH:11][C@H:12]1[C@@H:15]([S:16][CH2:17][C:18]([CH:20]2[CH2:24][CH2:23][CH2:22][S:21]2)=O)[N:14]([C:25](=P(CCCC)(CCCC)CCCC)[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:13]1=[O:46])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[O:1]([CH2:8][C:9]([NH:11][C@@H:12]1[C:13](=[O:46])[N:14]2[C:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[C:18]([CH:20]3[CH2:24][CH2:23][CH2:22][S:21]3)[CH2:17][S:16][C@H:15]12)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 131719838HCID 131719838, compound

Product 1

HCID 53921777HCID 53921777, compoundYield 21.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

t-Butyl 2-[(3R,4R)-3-phenoxyacetamido-4-[(RS)-tetrahydrothien-2-yl carbonylmethylthio]azetidin-2-on-1-yl]-2-tri-n-butylphosphoranylideneacetate (2.96 g) in toluene (100 ml) was heated under reflux for ca. 24 h. T.l.c. showed very small amounts of unchanged starting material. The solution was concentrated and flash chromatographed on silica gel eluting with 30, 40, 50 and 60% ethyl acetate/hexane. The first product to be eluted was the high Rf single diastereoisomer of the title compound (0.388 g, 19%) as a yellow foam; (Found: M+, 476.1442. C23H28N2O5S2 requires M, 476.1440); νmax (CH2Cl2) 3407, 1783, 1716 and 1698 cm-1 ; ΔH (CDCl3) 1.45-1.63 (10H, s overlapping m), 1.82-2.01 (1H, m), 2.21-2.33 (1H, m), 2.44-2.53 (1H, m), 2.97 (1H, dd, J 3.9, 8.8 Hz), 3.35 and 3.76 (2H, ABq, J 18.0 Hz), 4.57 (2H, s), 4.90 and 4.94 (1H, dd, J 6.5, 9.9 Hz), 5.01 (1H, d, J 4.8 Hz), 5.86 and 5.91 (1H, dd, J 4.8, 9.3 Hz), 6.85-7.07 (3H, m) and 7.24-7.36 (3H, m). The second product to be eluted was contaminated with an impurity. Re-chromatography of this material afford the low Rf diastereoisomer of the title compound (0.428 g, 21%); νmax (CH2Cl2) 3406, 1785, 1719 and 1697 cm-1 ; δH (CDCl3) 1.45-2.00 (11H, m overlapping s), 2.93-2.98 (2H, m), 3.45 and 3.56 (2H, ABq, J 17.3 Hz), 4.57 (2H, s), 4.84 (1H, dd, J 6.3, 10.0 Hz), 5.03 (1H, d, J 4.9 Hz), 5.88 (1H, dd, J 4.9, 12.7 Hz), 6.91-7.07 (3H, m) and 7.25-7.36 (3H, m).

Workup

  1. temperatureunder reflux for ca. 24 h
  2. concentrationThe solution was concentrated
  3. customflash chromatographed on silica gel eluting with 30, 40, 50 and 60% ethyl acetate/hexane
  4. washThe first product to be eluted
  5. washThe second product to be eluted

Sources & evidence

ORD record
ord-ca2fd7c342a4479f8f7259ccbfc390ec
Source dataset
uspto-grants-1997_02
Patent number
US05602117

Reaction notes

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