Lithium Hexamethyldisilazide → 7-(7-Hydroxy-6-oxo-2,3-dip-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid

HRID 406237Notes

Reaction equation

HRID 406237 reaction equation
[O:1]=[C:2]1[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])[C:6]2=[N:7][C:8]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[N:10]=[C:5]2[CH2:4][CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].CC1(C)C23[C@@]4(ON4S(=O)(=[O:53])C2)C(Cl)(Cl)[C@H]1CC3>C1COCC1>[OH:53][CH:3]1[C:2](=[O:1])[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])[C:6]2=[N:7][C:8]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=3)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=3)[N:10]=[C:5]2[CH2:4]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 16212295(6R,8S)-7,7-Dichloro-11,11-dimethyl-5-oxa-3lambda6-thia-4-azatetracyclo[6.2.1.01,6.04,6]undecane 3,3-dioxideHCID 666657007-(6-oxo-2,3-dip-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid

Product 1

HCID 666658047-(7-Hydroxy-6-oxo-2,3-dip-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-10 °C

Procedure

To a solution of 7-(6-oxo-2,3-dip-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid (Ex. 12.1) (100 mg, 0.219 mmol) in THF (2 ml), under a nitrogen atmosphere at −78° C., was treated dropwise with 1M lithium bis trimethylsilylamide in THF (0.5 ml, 0.500 mmol). Once the addition was complete, the mixture was stirred at −78° C. for 1 hour before a solution of (+)-(8,8-dichlorocamphorylsulfonyl)oxaziridine (78 mg, 0.262 mmol) in THF (2 ml) was added. The resultant solution was stirred at −78° C. for 60 minutes. The cooling was removed and the mixture allowed to warm to around −10° C. The mixture was allowed to slowly warm to room temperature overnight. The mixture was cooled to −78° C., quenched with sat. NH4Cl (3 ml) and allowed to slowly warm to room temperature. The yellow solution was diluted with water and extracted with EtOAc (×2). The aqueous layer (pH-9) was acidified to pH ˜2 with 1M HCl and extracted with DCM (×2). The combined organic extracts were dried (MgSO4) and evaporated under vacuum to give a yellow gum. The residue was purified by chromatography on silica eluting with 1% MeOH/DCM followed by 10% MeOH/DCM to afford the title compound;

Workup

  1. additionOnce the addition
  2. additionwas added
  3. customThe cooling was removed
  4. temperatureto slowly warm to room temperature overnight
  5. temperatureThe mixture was cooled to −78° C.
  6. customquenched with sat. NH4Cl (3 ml)
  7. temperatureto slowly warm to room temperature
  8. additionThe yellow solution was diluted with water
  9. extractionextracted with EtOAc (×2)
  10. extractionextracted with DCM (×2)
  11. dry with materialThe combined organic extracts were dried (MgSO4)
  12. customevaporated under vacuum
  13. customto give a yellow gum
  14. customThe residue was purified by chromatography on silica eluting with 1% MeOH/DCM

Sources & evidence

ORD record
ord-cb2e8b1ef9df4b39a34b9971063cb105
Source dataset
uspto-grants-2014_06
Patent number
US08754085B2

Reaction notes

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