Methyl chloroformate → HCID 118492082, compound

HRID 711342Notes

Reaction equation

HRID 711342 reaction equation
[CH3:1][N:2]([C@@H:22]([C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([CH3:34])[CH:25]=1)[CH3:23])[C:3]([N:5]1[CH2:10][CH2:9][N:8]2[C:11](=[O:14])[CH2:12][CH2:13][C@H:7]2[C@@H:6]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH3:21])=[O:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:45](Cl)(=[O:48])[O:46][CH3:47]>C1COCC1>[CH3:1][N:2]([C@@H:22]([C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([CH3:34])[CH:25]=1)[CH3:23])[C:3]([N:5]1[CH2:10][CH2:9][N:8]2[C:11](=[O:14])[C:12]([C:45]([O:46][CH3:47])=[O:48])([C:45]([O:46][CH3:47])=[O:48])[CH2:13][C@H:7]2[C@@H:6]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH3:21])=[O:4]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 71715371HCID 71715371, compound

Product 1

HCID 118492082HCID 118492082, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,8aS)-N-methyl-N-((R)-1-(3-methyl-5-(trifluoromethyl)phenyl)ethyl)-6-oxo-1-o-tolylhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxamide (350 mg, 0.74 mmol) in anhydrous THF (20 mL) under N2 atmosphere was added LHMDS (4.43 mL, 1 M in THF, 4.43 mmol) at −60° C. The reaction was stirred for 30 min followed by addition of methyl carbonochloridate (174 mg, 1.85 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 (200 mg, yield: 46%); m/z (ES+): 590 [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-911e577631c1466885bf91eaecc9ff4c
Source dataset
uspto-grants-2015_11
Patent number
US09181259B2

Reaction notes

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