Trifluoroacetic acid → Benzyl ((3R,4R)-4-fluoropyrrolidin-3-yl)carbamate

HRID 928197Notes

Reaction equation

HRID 928197 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[C@H:16]([F:17])[CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[F:17][C@@H:16]1[CH2:15][NH:14][CH2:13][C@H:12]1[NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 11430Potassium CarbonateHCID 118084914tert-butyl (3R,4R)-3-(benzyloxycarbonylamino)-4-fluoro-pyrrolidine-1-carboxylate

Product 1

HCID 96884550Benzyl ((3R,4R)-4-fluoropyrrolidin-3-yl)carbamateYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl (3R,4R)-3-{[(benzyloxy)carbonyl]amino}-4-fluoropyrrolidine-1-carboxylate (380 mg, 1.2 mmol) in DCM (20 mL) was added TFA (0.34 mL, 3.4 mmol, 3 mol eq). The resulting reaction was stirred at ambient temperature for 2 hr. More TFA (0.34 mL, 3.4 mmol, 3 mol eq) was added and stirring at ambient temperature continued for another 2 hr. The volatiles were removed to give a colorless residue. DCM (30 mL) and aqueous K2CO3 (1 M, 5 mL) were added. The organic layer was separated, extracted with more DCM (30 mL), dried over Na2SO4 and evaporated to give the title compound as a colorless gum (246 mg, 92% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.29-7.43 (m, 5 H) 4.80-5.21 (m, 4 H) 4.07-4.28 (m, 1 H) 3.46 (br. s., 1 H) 2.96-3.30 (m, 2 H) 2.74 (br. s., 1 H). 19F NMR (376 MHz, chloroform-d) δ ppm −72.38 (s, 1F). m/z (APCI+) for C12H15FN2O2 239.2 (M+H)+. Chiral purity was determined as below (using the racemic sample to compare):

Workup

  1. customThe resulting reaction
  2. stirringstirring at ambient temperature
  3. waitcontinued for another 2 hr
  4. customThe volatiles were removed
  5. customto give a colorless residue
  6. customThe organic layer was separated
  7. extractionextracted with more DCM (30 mL)
  8. dry with materialdried over Na2SO4
  9. customevaporated

Sources & evidence

ORD record
ord-d6ce4e26aad04e239e70167fa17134e6
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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