HCID 22171013, compound → HCID 58630661, compound

HRID 2376206Notes

Reaction equation

HRID 2376206 reaction equation
[C:1]1([CH3:23])[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([N:10]2[C@H:14]3[C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[CH2:21][C@H:13]3[O:12][C:11]2=[O:22])=[O:9])[CH:2]=1.C[Si](C)(C)N[Si](C)(C)C.[Na].[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[N:46]([C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)[N:45]=[C:44]([CH2:55]I)[CH:43]=2)[CH:38]=[CH:39][C:40]=1[Cl:41]>C1COCC1>[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[N:46]([C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)[N:45]=[C:44]([CH2:55][C@@H:7]([C:3]3[CH:2]=[C:1]([CH3:23])[CH:6]=[CH:5][CH:4]=3)[C:8]([N:10]3[C@H:14]4[C:15]5[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=5[CH2:21][C@H:13]4[O:12][C:11]3=[O:22])=[O:9])[CH:43]=2)[CH:38]=[CH:39][C:40]=1[Cl:41]

Participants

5

Reactant 3

HCID 22171013HCID 22171013, compound2×HCID 45051731Sodium hexamethyidisilazaneHCID 58630654HCID 58630654, compound2×

Product 1

HCID 58630661HCID 58630661, compoundYield 83.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of (3aS,8aR)-3-(2-m-tolyl-acetyl)-3,3a,8,8a-tetrahydro-indeno[1,2-d]oxazol-2-one (product of Step F., 12 g, 0.039 mol) in THF (100 mL) was added 1.0 M sodium 1,1,1,3,3,3-hexamethyldisilazane (NaHMDS) (41 mL, 0.041 mol) in THF at −78° C. The mixture was stirred for 45 min at −78° C. then treated with 5-(3,4-dichloro-phenyl)-3-iodomethyl-1-(4-methoxy-phenyl)-1l-H-pyrazole (product of Step E., 18.4 g, 0.0405 mol) in THF (100 mL). The reaction mixture was allowed to warm to rt overnight and then was quenched with H2O (100 mL) and concentrated to half the volume. The aqueous layer was washed with EtOAc (3×75 mL). The extracted organic layer was washed with saturated NaCl, dried over Na2SO4, filtered and concentrated to an oil. The crude oil was purified by flash column chromatography (silica gel, 7:3 hexane/EtOAc) to obtain 20.7 g of the title compound (83%) as white foam. HPLC: Rt=11.38 (Method E). MS (ES+): mass calculated for C36H29Cl2N3O4, 638.55; m/z found 660.3 [M+Na]+. 1H NMR (400 MHz, CDCl3): 7.52 (d, J=7.6 Hz, 1H), 7.11-7.35 (m, 8H), 6.93-6.99 (m, 3H), 6.74-6.82 (m, 3H), 6.20 (s, 1H), 5.89 (d, J=6.8 Hz, 1H), 5.58 (q, J=6.1, 4.5 Hz, 1H), 5.11-5.15 (m, 1H), 3.8 (s, 3H), 3.72 (dd, J=10.6, 4.1 Hz, 1H), 3.33 (br, s, 2H), 3.07 (dd, J=9.8, 4.8 Hz, 1H), 2.37 (s, 3H).

Workup

  1. temperatureto warm to rt overnight
  2. customwas quenched with H2O (100 mL)
  3. concentrationconcentrated to half the volume
  4. washThe aqueous layer was washed with EtOAc (3×75 mL)
  5. washThe extracted organic layer was washed with saturated NaCl
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to an oil
  9. customThe crude oil was purified by flash column chromatography (silica gel, 7:3 hexane/EtOAc)

Sources & evidence

ORD record
ord-c561acb9347245b79a01a53485323e89
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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