Methyl chloroformate → HCID 42633348, compound

HRID 409427Notes

Reaction equation

HRID 409427 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][CH3:14])[CH2:11][C@H:10]([NH:15][CH2:16][C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([C:27]([F:30])([F:29])[F:28])[CH:18]=2)[C@@H:9]1[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:45]([O:47][CH3:48])=[O:46].CCOC(C)=O>C(#N)C.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][CH3:14])[CH2:11][C@H:10]([N:15]([CH2:16][C:17]2[CH:22]=[C:21]([C:23]([F:25])([F:24])[F:26])[CH:20]=[C:19]([C:27]([F:30])([F:28])[F:29])[CH:18]=2)[C:45]([O:47][CH3:48])=[O:46])[C@@H:9]1[CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 6586Methyl chloroformate2×HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 59614365HCID 59614365, compound

Product 1

HCID 42633348HCID 42633348, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (2S,3S,5R)-2-benzyl-3-(3,5-bis-trifluoromethyl-benzylamino)-5-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.0377 mmol; 20 mg) and cesium carbonate (0.113 mmol; 36.8 mg) in acetonitrile (0.38 mL) is added methyl chloroformate (0.0754 mmol; 5.9 mg) at room temperature. The reaction mixture is warmed to 80° C. and stirred for 3.5 hours. Additional methyl chloroformate (0.0754 mmol; 5.9 mg) is added to the mixture, and the mixture is stirred for additional 0.5 hours, and then cooled to room temperature. To the mixture is added brine and EtOAc. The organic layer is separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by preparative thin layer chromatography on silica gel (eluent: n-hexane/EtOAc) to give (2S,3S,5R)-2-Benzyl-3-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-5-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (11.5 mg, 52%); ESI-MS m/z: 589 [M+1]+, Retention time 2.63 min (condition A).

Workup

  1. stirringthe mixture is stirred for additional 0.5 hours
  2. temperaturecooled to room temperature
  3. customThe organic layer is separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by preparative thin layer chromatography on silica gel (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-5e7054397440409c987ff509d9abb056
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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