Triethylamine → 4-(3-tert-Butoxycarbonylaminopyrrolidin-1-yl)-2,5-difluorobenzoic acid ethyl ester

HRID 10287Notes

Reaction equation

HRID 10287 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([F:11])[C:8](F)=[CH:7][C:6]=1[F:13])[CH3:2].C(N(CC)CC)C.[C:22]([O:26][C:27](=[O:34])[NH:28][CH:29]1[CH2:33][CH2:32][NH:31][CH2:30]1)([CH3:25])([CH3:24])[CH3:23]>C(#N)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([N:31]2[CH2:32][CH2:33][CH:29]([NH:28][C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:34])[CH2:30]2)=[CH:7][C:6]=1[F:13])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 2774397Benzoic acid, 2,4,5-trifluoro-, ethyl ester

Product 1

HCID 690751024-(3-tert-Butoxycarbonylaminopyrrolidin-1-yl)-2,5-difluorobenzoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2,4,5-trifluorobenzoic acid ethyl ester (Example 1e, 14.8 g, 72.4 mmol) in acetonitrile (225 mL) is added triethylamine (65 mL, 466 mmol) and pyrrolidin-3-ylcarbamic acid tert-butyl ester (16.07 g, 86.2 mmol). After 45 hours, the reaction mixture is diluted with ethyl acetate and washed with saturated NaHCO3, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate is concentrated to afford an oil. The resulting residue is purified by flash chromatography (1:5 ethyl acetate/hexanes) to afford the title compound. MS (ES, M+1) m/z 371, mp 98–100° C.

Workup

  1. washwashed with saturated NaHCO3, water, and brine
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate is concentrated
  5. customto afford an oil
  6. customThe resulting residue is purified by flash chromatography (1:5 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0a282666be1a4e63bfa975c0f623bbd3
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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