Sodium Bicarbonate → HCID 58573946, compound

HRID 932290Notes

Reaction equation

HRID 932290 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:30][CH3:31])[CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][S:24]3(=[O:29])=[O:28])[C:11](=[O:32])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C([Li])(CC)C.I[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[N:41]=1.C(=O)(O)[O-].[Na+]>C1COCC1.C1CCCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([C@@H:21]([CH2:30][CH3:31])[CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][S:24]3(=[O:29])=[O:28])[C:11](=[O:32])[C@H:10]([CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[N:41]=3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 58573628HCID 58573628, compoundHCID 86707915HCID 86707915, compoundHCID 178418400CID 53628100

Product 1

HCID 58573946HCID 58573946, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(1,1-dioxidoisothiazolidin-2-yl)butan-2-yl)piperidin-2-one (Example 420, Step A, 0.7 g, 1.413 mmol) in THF (5.65 ml) at −78° C. was added dropwise sec-butyllithium, (1.4 M in cyclohexane, 1.06 ml, 1.483 mmol). The reaction was warmed to −10° C. After about 5 minutes, the reaction was returned to a −78° C. bath. A solution of 2-(iodomethyl)-6-methoxypyridine (Example 420, Step B, 0.387 g, 1.554 mmol) in THF (1 mL) was added dropwise to the cooled reaction mixture. The reaction was allowed to warm to room temperature and stirred for 1 h. The reaction contents were poured into saturated sodium bicarbonate and the aqueous layer was extracted with dichloromethane (3×50 mL). The combined organics were dried with sodium sulfate and concentrated in vacuo. Silica gel chromatography (step gradient elution 5 to 50% diethyl ether in dichloromethane) afforded the title compound as the more polar diastereomer.

Workup

  1. customwas returned to a −78° C.
  2. temperatureto warm to room temperature
  3. customThe reaction contents
  4. extractionthe aqueous layer was extracted with dichloromethane (3×50 mL)
  5. dry with materialThe combined organics were dried with sodium sulfate
  6. concentrationconcentrated in vacuo
  7. washSilica gel chromatography (step gradient elution 5 to 50% diethyl ether in dichloromethane)

Sources & evidence

ORD record
ord-26f504056a394d0982b3f9d03863a4cb
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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