Trifluoroacetic acid → Phenylmethyl {[(3R,4S)-4-hydroxy-3-pyrrolidinyl]methyl}carbamate

HRID 657023Notes

Reaction equation

HRID 657023 reaction equation
[OH:1][C@H:2]1[C@@H:6]([CH2:7][NH:8][C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.FC(F)(F)C(O)=O.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>C(Cl)Cl>[OH:1][C@@H:2]1[CH2:3][NH:4][CH2:5][C@@H:6]1[CH2:7][NH:8][C:9](=[O:10])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 59254350rac-tert-butyl (3R,4R)-3-({[(benzyloxy)carbonyl]amino}methyl)-4-hydroxypyrrolidine-1-carboxylate2×

Product 1

HCID 59026130Phenylmethyl {[(3R,4S)-4-hydroxy-3-pyrrolidinyl]methyl}carbamateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1,1-dimethylethyl (3S,4S)-3-hydroxy-4-[({[(phenylmethyl)oxy]carbonyl}amino)methyl]-1-pyrrolidinecarboxylate (for a synthesis see WO2006002047 preparation 24(c), (±)-1,1-dimethylethyl cis-3-hydroxy-4-[({[(phenylmethyl)oxy]carbonyl}amino)methyl]-1-pyrrolidinecarboxylate E1 isomer) (1 g, 2.85 mmol) in DCM (50 ml) was added trifluoracetic acid (50 ml) and stirred for 2 h. The reaction mixture was concentrated and placed under high vacuum for 3 h. To the TFA salt dissolved in DCM (50 ml) was added MP-carbonate resin (4 g; 11.4 mmol) and stirred overnight. The reaction mixture was filtered and concentrated to provide the title compound as a pale yellow oil (840 mg, 100%)

Workup

  1. concentrationThe reaction mixture was concentrated
  2. waitplaced under high vacuum for 3 h
  3. dissolutionTo the TFA salt dissolved in DCM (50 ml)
  4. stirringstirred overnight
  5. filtrationThe reaction mixture was filtered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-95e54f6eefa846ffba3c379d95b90f18
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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