Triphenylphosphine → 2-[1-(4-Amino-phenyl)-2,2,2-trifluoro-1-trifluoromethyl-ethoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2247294Notes

Reaction equation

HRID 2247294 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH:26]1[CH2:30]O)=[O:24])([CH3:21])([CH3:20])[CH3:19].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH:26]1[CH2:30][O:17][C:8]([C:5]1[CH:4]=[CH:3][C:2]([NH2:1])=[CH:7][CH:6]=1)([C:9]([F:10])([F:11])[F:12])[C:13]([F:14])([F:15])[F:16])=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 550865tert-Butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylateHCID 5778012-(4-Aminophenyl)-1,1,1,3,3,3-hexafluoropropan-2-olHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 865903822-[1-(4-Amino-phenyl)-2,2,2-trifluoro-1-trifluoromethyl-ethoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-(4-amino-phenyl)-1,1,1,3,3,3-hexafluoro-propan-2-ol (1.30 g), 2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.00 g), PPh3 (1.56 g) and molecular sieves 4 Å in THF (100 mL) was added DEAD (0.93 mL) slowly. The reaction was stirred at RT for 5 h and at reflux for overnight. After filtration to remove solids, the filtrate was concentrated and the residue was taken into ether. The organic phase was washed with saturated NaHCO3 and brine. The organic layer was dried over MgSO4 and evaporated to give a crude product as a very viscous brown oil which was chromatographed through silica gel (400 g, 2:1:7 to 3:1:6 EtOAc/Et3N/hexanes) to afford 2-[1-(4-amino-phenyl)-2,2,2-trifluoro-1-trifluoromethyl-ethoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester as a light brown oil.

Workup

  1. temperatureat reflux for overnight
  2. filtrationAfter filtration
  3. customto remove solids
  4. concentrationthe filtrate was concentrated
  5. washThe organic phase was washed with saturated NaHCO3 and brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. customevaporated
  8. customto give a crude product as a very viscous brown oil which
  9. customwas chromatographed through silica gel (400 g, 2:1:7 to 3:1:6 EtOAc/Et3N/hexanes)

Sources & evidence

ORD record
ord-28bca9b04e8c4923b9344bfaedd9bc84
Source dataset
uspto-grants-2010_03
Patent number
US07687643B2

Reaction notes

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