Tetrabutylammonium Fluoride → Tert-butyl(2S,5R)-2-[(6-aminopyridin-3-yl)methyl]-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1 carboxylate

HRID 713702Notes

Reaction equation

HRID 713702 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C@@H:9]2[CH2:13][CH2:12][C@H:11]([C@H:14]([O:21][Si](C(C)(C)C)(C)C)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:10]2[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:4][CH:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C@@H:9]2[CH2:13][CH2:12][C@H:11]([C@H:14]([OH:21])[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:10]2[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 123603902Tert-butyl(2S,5R)-2-[(6-aminopyridin-3-yl)methyl]-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pyrrolidine-1-carboxylate

Product 1

HCID 117653175Tert-butyl(2S,5R)-2-[(6-aminopyridin-3-yl)methyl]-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1 carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution tert-butyl(2S,5R)-2-[(6-aminopyridin-3-yl)methyl]-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pyrrolidine-1-carboxylate (40 mg, 0.08 mmol) in THF (0.5 mL) was added 1.0M solution of TBAF in THF (1 mL, 1.0 mmol) and the resulting solution stirred for an hour at room temperature. The mixture was concentrate under vacuum and the residue taken up in dichloromethane (10 mL). The solution was washed with water (5 mL) and brine (5 mL). The organics were then dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was purified vial preparative TLC plate (1000 μM) eluting with 5% methanol in dichloromethane to afford the title compound as a white foam (25.2 mg, 92%). LC-MS: C22H29N3O3 calculated 338.23 found m/z (ES) 339.2 (MH) and 239.2 (M-Boc)+.

Workup

  1. concentrationThe mixture was concentrate under vacuum
  2. washThe solution was washed with water (5 mL) and brine (5 mL)
  3. dry with materialThe organics were then dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified vial preparative TLC plate (1000 μM)
  7. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-60ba06b8d0004ff39d4f2da75f12bd7c
Source dataset
uspto-grants-2015_11
Patent number
US09186354B2

Reaction notes

Loading…