Tert-Butylamine → tert-butyl (2R,5S)-2-[(R)-[6-(tert-butylamino)pyridin-3-yl]{[tert-butyl(dimethyl)silyl]oxy}methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate

HRID 1911849Notes

Reaction equation

HRID 1911849 reaction equation
[Si:1]([O:8][C@H:9]([C:33]1[CH:34]=[N+:35]([O-])[CH:36]=[CH:37][CH:38]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:17]=2)[N:11]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:40]([NH2:44])([CH3:43])([CH3:42])[CH3:41].C1(C)C=CC(S(OS(C2C=CC(C)=CC=2)(=O)=O)(=O)=O)=CC=1>FC(F)(F)C1C=CC=CC=1.CCOC(C)=O>[C:40]([NH:44][C:36]1[N:35]=[CH:34][C:33]([C@@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[C@H:10]2[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:17]=3)[N:11]2[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:38][CH:37]=1)([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 3

HCID 6385Tert-ButylamineHCID 77773Toluene-p-sulphonic anhydrideHCID 86670463tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(1-oxidopyridin-3-yl)methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate

Product 1

HCID 86670465tert-butyl (2R,5S)-2-[(R)-[6-(tert-butylamino)pyridin-3-yl]{[tert-butyl(dimethyl)silyl]oxy}methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylateYield 88.3%

Reagents, catalysts & solvents 2

HCID 7368(Trifluoromethyl)benzeneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(1-oxidopyridin-3-yl)methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate (0.049 g, 0.087 mmol) in trifluorotoluene (2 mL) was cooled to 0° C. Tert-butylamine (0.046 mL, 0.44 mmol) was added, followed by p-toluenesulfonic anhydride (0.057 g, 0.18 mmol). After 1 hour, the reaction was diluted with EtOAc (50 mL) and washed with water (15 mL) and brine (15 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography with 0-45% EtOAc/hexanes to afford 47 mg of impure tert-butyl (2R,5S)-2-[(R)-[6-(tert-butylamino)pyridin-3-yl]{[tert-butyl(dimethyl)silyl]oxy}methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate. LC-MS=6123 (M−H)+.

Workup

  1. washwashed with water (15 mL) and brine (15 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography with 0-45% EtOAc/hexanes

Sources & evidence

ORD record
ord-7fd9c2ea4c14400f877e6bcfb24fe5a1
Source dataset
uspto-grants-2013_12
Patent number
US08604038B2

Reaction notes

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