HCID 46932578, compound → HCID 66680964, compound

HRID 1844378Notes

Reaction equation

HRID 1844378 reaction equation
CON(C)[C:4]([C@@H:6]1[C:9](=[O:10])[N:8]([C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@H:7]1[CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:5].[CH3:36][Mg+].[Br-]>CCOC(C)=O>[C:4]([C@H:6]1[C:9](=[O:10])[N:8]([C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@H:7]1[CH2:30][C:31]([O:33][CH3:34])=[O:32])(=[O:5])[CH3:36]

Participants

4

Reactant 2

HCID 46932578HCID 46932578, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 66680964HCID 66680964, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Oven-dried LiC1 (0.276 g, 6.511 mmol, 7.3 equiv) was vigorously stirred in THF (9.0 mL) until fully dissolved. Trans β-lactam 15 (0.420 g, 0.889 mmol, 1.0 equiv) was added and cooled to 0° C. A solution of MeMgBr (0.98 mL, 0.987 mmol, 1.1 equiv, 1M THF) was added dropwise and stirred at 0° C. for 2 h, at which time the ice-bath was removed and the reaction allowed to slowly warm to room temperature. After stirring for 48 h sat. NHCl(aq) was added to quench the reaction, which was further diluted with EtOAc. The organics were washed with water, followed by brine and dried over Na2SO4. The organics were concentrated in vacuo and purified by flash column chromatography (35% EtOAc/hexanes) to provide the pure ketone 16 (Rf=0.32, 0.135 g, 36% yield) and recovered starting material 15 (Rf=0.16, 0.249 g) representing an 87% yield (based on recovered starting material, brsm). m.p.=52-54° C.; [α]D23=+71.875° (c=0.8, MeOH); 1H NMR (500 MHz, CDCl3): δ 7.31-7.36 (m, 9H); 7.20-7.22 (m, 6H); 5.41 (ddd, J=2.2, 3.5, 10.3 Hz, 1H); 4.03 (d, J=2.1 Hz, 1H); 3.57 (s, 3H); 2.36 (s, 3H); 2.13 (dd, J=10.3, 16.2 Hz, 1H); 1.73 (dd, J=3.5, 16.2 Hz, H); 13C NMR (125 MHz, CDCl3): δ 200.04, 170.45, 163.17, 141.83, 129.82, 128.26, 128.00, 74.54, 66.68, 52.01, 52.01, 37.15, 30.70; IR (thin film): 3059, 2953, 1759, 1714, 1597, 1493, 1444, 1359, 1337, 1177, 1034, 752, 700, 639 cm−1; HRMS for [M+Na]C27H25NO4Na calc'd., 450.16758, found, 450.16980 (Error=4.9322 ppm).

Workup

  1. customOven-dried LiC1 (0.276 g, 6.511 mmol, 7.3 equiv)
  2. dissolutionuntil fully dissolved
  3. customwas removed
  4. temperatureto slowly warm to room temperature
  5. stirringAfter stirring for 48 h sat. NHCl(aq)
  6. additionwas added
  7. customto quench
  8. customthe reaction, which
  9. washThe organics were washed with water
  10. dry with materialdried over Na2SO4
  11. concentrationThe organics were concentrated in vacuo
  12. custompurified by flash column chromatography (35% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ed8d7eae77094eb880410e9b20b15eb7
Source dataset
uspto-grants-2015_02
Patent number
US08946408B2

Reaction notes

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