Methyl chloroformate → HCID 118491993, compound

HRID 711343Notes

Reaction equation

HRID 711343 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:35])[C:16]([N:18]2[CH2:23][CH2:22][N:21]3[C:24](=[O:27])[CH2:25][CH2:26][C@H:20]3[C@@H:19]2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[CH3:34])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:48](Cl)(=[O:51])[O:49][CH3:50]>C1COCC1>[F:37][C:2]([F:1])([F:36])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:35])[C:16]([N:18]2[CH2:23][CH2:22][N:21]3[C:24](=[O:27])[C:25]([C:48]([O:49][CH3:50])=[O:51])([C:48]([O:49][CH3:50])=[O:51])[CH2:26][C@H:20]3[C@@H:19]2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[CH3:34])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 71680612HCID 71680612, compound

Product 1

HCID 118491993HCID 118491993, compoundYield 45.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,8aS)-N-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethyl)-N-methyl-6-oxo-1-o-tolylhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxamide (300 mg, 0.57 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 EA (2×50 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 (166 mg, yield: 45.3%); m/z (ES+): 644 [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 EA (2×50 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-656363cfd7624bd099a0c581f59560a3
Source dataset
uspto-grants-2015_11
Patent number
US09181259B2

Reaction notes

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