Trifluoroacetic acid → HCID 12021270, compound

HRID 1058314Notes

Reaction equation

HRID 1058314 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:31][N:32]2[CH2:35][CH:34]([OH:36])[CH2:33]2)=[C:13]([CH:30]=1)[CH2:14][NH:15][C:16](=[O:29])[C@@H:17]1[CH2:21][CH2:20][CH2:19][N:18]1C(OC(C)(C)C)=O>C(Cl)Cl>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:31][N:32]2[CH2:35][CH:34]([OH:36])[CH2:33]2)=[C:13]([CH:30]=1)[CH2:14][NH:15][C:16](=[O:29])[C@@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69939642HCID 69939642, compound

Product 1

HCID 12021270HCID 12021270, compoundYield 35.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (3 mL) was added to a stirred solution of N-{5-chloro-2-[(3-hydroxyazetidin-1-yl)methyl]benzyl}-1-(tert-butoxycarbonyl)-L-prolinamide (210 mg, 0.49 mmol) in CH2Cl2 (6 mL) at 0° C. After 90 min the solution was concentrated and the residue was partitioned between CH2Cl2 and 10% NaHCO3. The aqueous layer was saturated with NaCl and then extracted with more CH2Cl2. The combined organic layers were washed with brine, dried over (Na2SO4) and then evaporated. The reside was purified by chromatography on silica (ammonia saturated CHCl3/MeOH, 93:7) to give N-{5-chloro-2-[(3-hydroxyazetidin-1-yl)methyl]benzyl}-L-prolinamide (55.8 mg) as a glass: 1H NMR (CDCl3, 400 MHz) δ 1.71 (m, 2H), 1.93 (m, 1H), 2.16 (m, 1H), 2.92 (m, 2H), 3.05 (m, 2H), 3.39 (m, 2H), 3.61 (dd, J=12.3, 20.7 Hz, 2H), 3.72 (dd, J=6.4, 8.6 Hz, 2H), 4.28-4.46 (m, 3H), 7.12 (d, J=8.1 Hz), 7.19 (dd, J=2.2, 8.1 Hz), 7.36 (d, J=2.0 Hz, 1H), 9.09 (br s, 1H).

Workup

  1. concentrationAfter 90 min the solution was concentrated
  2. customthe residue was partitioned between CH2Cl2 and 10% NaHCO3
  3. extractionextracted with more CH2Cl2
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over (Na2SO4)
  6. customevaporated
  7. customThe reside was purified by chromatography on silica (ammonia saturated CHCl3/MeOH, 93:7)

Sources & evidence

ORD record
ord-ba27fb06bc4f42b2ad7d0fe18cf90ac3
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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