Methyl chloroformate → HCID 118491993, compound

HRID 711344Notes

Reaction equation

HRID 711344 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C@H:12]([N:14]([CH3:34])[C:15]([N:17]2[CH2:22][CH2:21][N:20]3[C:23](=[O:26])[CH2:24][CH2:25][C@H:19]3[C@@H:18]2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[O:16])[CH3:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:45](Cl)(=[O:48])[O:46][CH3:47]>C1COCC1>[F:9][C:8]([F:11])([F:10])[C:2]1[CH:3]=[C:4]([C@H:12]([N:14]([CH3:34])[C:15]([N:17]2[CH2:22][CH2:21][N:20]3[C:23](=[O:26])[C:24]([C:45]([O:46][CH3:47])=[O:48])([C:45]([O:46][CH3:47])=[O:48])[CH2:25][C@H:19]3[C@@H:18]2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[O:16])[CH3:13])[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 118492065HCID 118492065, compound

Product 1

HCID 118491993HCID 118491993, compoundYield 112.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,8aS)-N-((R)-1-(3-chloro-5-(trifluoromethyl)phenyl)ethyl)-N-methyl-6-oxo-1-o-tolylhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxamide (300 mg, 0.61 mmol) in anhydrous THF (20 mL) under N2 atmosphere was added LiHMDS (2.3 mL, 1 M in THF, 2.3 mmol) at −60° C. The reaction was stirred for 30 min followed by addition of methyl carbonochloridate (134 mg, 1.43 mmol). After stirring for another 3 h at room temperature, the reaction was quenched with water at 0° C. and then extracted with EtOAc (2×30 mL). The combined organic layers were dried over anhydrous Na2SO4 and then concentrated in high vacuum. The residue was purified by silica gel chromatography (DCM/MeOH=20/1 to 10/1) to give the title compound (220 mg, yield: 59%); m/z (ES+): 610 [M+H]+.

Workup

  1. stirringAfter stirring for another 3 h at room temperature
  2. customthe reaction was quenched with water at 0° C.
  3. extractionextracted with EtOAc (2×30 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. concentrationconcentrated in high vacuum
  6. customThe residue was purified by silica gel chromatography (DCM/MeOH=20/1 to 10/1)

Sources & evidence

ORD record
ord-02920aa3b1ed4cd0a4298dad7ed171ec
Source dataset
uspto-grants-2015_11
Patent number
US09181259B2

Reaction notes

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