Lithium Hexamethyldisilazide → HCID 86688227, compound

HRID 536456Notes

Reaction equation

HRID 536456 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C@H:6]([NH2:15])[CH2:7][C:8]([CH2:13][F:14])([CH3:12])[O:9]2)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C@H:6]([NH2:15])[CH2:7][C@:8]([CH2:13][F:14])([CH3:12])[O:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 68596917HCID 68596917, compound

Product 1

HCID 86688227HCID 86688227, compoundYield 32.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4R)-7-chloro-2-(fluoromethyl)-2-methylchroman-4-amine (2.21 g, 9.62 mmol) in THF (10 ml) was cooled to 0° C. Lithium bis(trimethylsilyl)amide (1M in THF, 20.2 mL, 20.2 mmol) was added slowly and the reaction was warmed to room temperature. After 4 hours, the reaction mixture was diluted with EtOAc (200 mL) and washed with 2N NaOH (50 mL) and brine (50 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The crude product was purified on SiO2 (3% MeOH/EtOAc) to give the title compound (715 mg, 32%). MS (ESI+) M/Z 230 (M+H)+

Workup

  1. washwashed with 2N NaOH (50 mL) and brine (50 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified on SiO2 (3% MeOH/EtOAc)

Sources & evidence

ORD record
ord-f4f905a717d446e1b05ff9fe0578156a
Source dataset
uspto-grants-2014_10
Patent number
US08859584B2

Reaction notes

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