Triethylamine → HCID 57651901, compound

HRID 1510273Notes

Reaction equation

HRID 1510273 reaction equation
[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[C:25]([O:29][C:30]([N:32]1[CH2:36][CH2:35][C@H:34]([O:37][C:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=2)[CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(N(CC)CC)C>ClCCl.CN(C=O)C>[C:25]([O:29][C:30]([N:32]1[CH2:36][CH2:35][C@H:34]([O:37][C:38]2[CH:43]=[CH:42][C:41]([NH:44][C:12]([C:10]3[N:11]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[O:8][C:9]=3[C:15]([F:18])([F:17])[F:16])=[O:14])=[CH:40][CH:39]=2)[CH2:33]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acidHCID 25632275tert-Butyl (3S)-3-(4-aminophenoxy)pyrrolidine-1-carboxylate

Product 1

HCID 57651901HCID 57651901, compoundYield 85.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

2-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (2.57 g, 10 mmol) was suspended in dichloromethane (20 mL). Oxalyl chloride (2M in dichloromethane, 10 mL) was added followed by DMF (0.028 mL). The mixture was stirred for 1 hr and solvents were evaporated. The residue was treated with benzene (20 mL) and solvents were evaporated. The residue was dissolved in dichloromethane (30 mL) and treated with a mixture of (S)-3-(4-amino-phenoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (2.78 g, 10 mmol) and triethylamine (3.6 mL, 25 mmol) under ice bath. The mixture was stirred for 30 minutes and ice bath was removed. The solution was further stirred for 2 hrs. Solvents were evaporated and the residue was extracted with 0.1N hydrochloric acid and ethyl acetate. The organic layer was washed with water, concentrated sodium bicarbonate solution and brine. Solvents were evaporated and the residue was purified through ISCO column chromatography (silica gel, ethyl acetate in hexanes, 10% to 80% linear gradient) to give (S)-3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-pyrrolidine-1-carboxylic acid tert-butyl ester (4.4 g, 85.1% yield). LC-MS for C26H26F3N3O5 (m/e) calcd 517, obsd 516 (M−H).

Workup

  1. customsolvents were evaporated
  2. additionThe residue was treated with benzene (20 mL) and solvents
  3. customwere evaporated
  4. dissolutionThe residue was dissolved in dichloromethane (30 mL)
  5. stirringThe mixture was stirred for 30 minutes
  6. customice bath was removed
  7. stirringThe solution was further stirred for 2 hrs
  8. customSolvents were evaporated
  9. extractionthe residue was extracted with 0.1N hydrochloric acid and ethyl acetate
  10. washThe organic layer was washed with water, concentrated sodium bicarbonate solution and brine
  11. customSolvents were evaporated
  12. customthe residue was purified through ISCO column chromatography (silica gel, ethyl acetate in hexanes, 10% to 80% linear gradient)

Sources & evidence

ORD record
ord-6000859a9eed4f0c8d93d3e420d504bd
Source dataset
uspto-grants-2012_07
Patent number
US08211914B2

Reaction notes

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