HCID 131727744, compound → HCID 131727743, compound

HRID 1434471Notes

Reaction equation

HRID 1434471 reaction equation
[CH2:1]([O:41][CH:42]1[C@H:46]2[C@H:47]([O:67][Si:68]([C:71]([CH3:74])([CH3:73])[CH3:72])([CH3:70])[CH3:69])[N:48]([C:59]([O:61][CH2:62][C:63]([Cl:66])([Cl:65])[Cl:64])=[O:60])[C:49]3[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][C:50]=3[C:51](=[O:52])[N:45]2[CH2:44][C@H:43]1[OH:75])[CH2:2][CH2:3][CH2:4][CH2:5][O:6][CH:7]1[C@H:11]2[C@H:12]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[N:13]([C:24]([O:26][CH2:27][C:28]([Cl:31])([Cl:30])[Cl:29])=[O:25])[C:14]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:15]=3[C:16](=[O:17])[N:10]2[CH2:9][C@H:8]1[OH:40]>C(Cl)Cl>[CH2:5]([O:6][CH:7]1[C@H:11]2[C@H:12]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[N:13]([C:24]([O:26][CH2:27][C:28]([Cl:29])([Cl:31])[Cl:30])=[O:25])[C:14]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:15]=3[C:16](=[O:17])[N:10]2[CH2:9][C:8]1=[O:40])[CH2:4][CH2:3][CH2:2][CH2:1][O:41][CH:42]1[C@H:46]2[C@H:47]([O:67][Si:68]([C:71]([CH3:72])([CH3:73])[CH3:74])([CH3:69])[CH3:70])[N:48]([C:59]([O:61][CH2:62][C:63]([Cl:66])([Cl:65])[Cl:64])=[O:60])[C:49]3[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][C:50]=3[C:51](=[O:52])[N:45]2[CH2:44][C:43]1=[O:75]

Participants

3

Reactant 1

HCID 131727744HCID 131727744, compound

Product 1

HCID 131727743HCID 131727743, compoundYield 57.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-55 °C

Procedure

After stirring at −55° C. for 15 minutes, a slurry of the substrate 42 (962 mg, 0.80 mmol) in dry DCM (8 mL) was added dropwise over a period of 10 minutes to the reaction mixture. After stirring for a further 1 h at −55° C., a solution of TEA (1.56 mL, 1.13 g; 11.2 mmol) in dry DCM (4 mL) was added dropwise over a period of 5 minutes to the reaction mixture. The reaction mixture was allowed to warm to 0° C. and then diluted with DCM (50 mL). The organic solution was washed with cold 1 N HCl (20 mL), H2O (20 mL), brine (30 mL) and dried (MgSO4). Filtration and evaporation of the solvent in vacuo afforded the crude product which was purified by flash column chromatography (50:50 v/v Hexane/EtOAc) to afford bis-ketone 43 as a foam (550 mg, 57%): 1H NMR (400 MHz, CDCl3) δ 7.25 (s, 2H), 6.76 (s, 2H), 5.82 (d, 2H, J=9.3 Hz), 5.22 (d, 2H, J=12.0 Hz), 4.32 (d, 2H, J=20.4 Hz), 4.22 (d, 2H, J=12.0 Hz), 4.17-4.08 (m, 4H), 4.03-3.89 (m, 10H), 2.96 (dd, 2H, J=19.6, 10.2 Hz), 2.56 (dd, 2H, J=19.6, 2.8 Hz), 1.99-1.92 (m, 4H), 1.72-1.64 (m, 2H), 0.86 (s, 18H), 0.24 and 0.23 (s×2, 12H); 13C NMR (100 MHz, CDCl3) δ 207.7, 168.0, 153.8, 151.0, 149.5, 127.9, 124.4, 114.1, 110.8, 95.2, 87.5, 74.8, 68.8, 58.9, 56.2, 52.9, 40.4, 28.7, 25.6, 22.8 17.8, −4.12 and −5.31.

Workup

  1. stirringAfter stirring for a further 1 h at −55° C.
  2. temperatureto warm to 0° C.
  3. washThe organic solution was washed with cold 1 N HCl (20 mL), H2O (20 mL), brine (30 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationFiltration and evaporation of the solvent in vacuo
  6. customafforded the crude product which
  7. customwas purified by flash column chromatography (50:50 v/v Hexane/EtOAc)

Sources & evidence

ORD record
ord-fa910fab65b744ff8c061d9c97f01af8
Source dataset
uspto-grants-2009_11
Patent number
US07612062B2

Reaction notes

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