Diisopropylethylamine → (S)-ethyl 1-((S)-2-(tert-butoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

HRID 627055Notes

Reaction equation

HRID 627055 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C)C(F)=[N+](C)C.[NH:43]1[C:47]2=[N:48][CH:49]=[CH:50][CH:51]=[C:46]2[CH2:45][C@H:44]1[C:52]([O:54][CH2:55][CH3:56])=[O:53]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:10]([N:43]1[C:47]2=[N:48][CH:49]=[CH:50][CH:51]=[C:46]2[CH2:45][C@H:44]1[C:52]([O:54][CH2:55][CH3:56])=[O:53])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 25260122(S)-2-((tert-Butoxycarbonyl)amino)-2-(tetrahydro-2H-pyran-4-yl)acetic acidHCID 121216118(S)-ethyl 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Product 1

HCID 131735271(S)-ethyl 1-((S)-2-(tert-butoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylateYield 48.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 100 mL round-bottomed flask, (S)-2-(tert-butoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid (270 mg, 1.04 mmol, Eq: 1.00) was combined with DCM (10 mL) to give a colorless solution. Diisopropylethylamine (0.73 mL, 4.16 mmol, Eq: 4) was added followed by N,N,N′,N′-tetramethylfluoroformamidinium hexafluorophosphate (824 mg, 3.12 mmol, Eq: 3). The reaction was stirred at rt for 1 h and then (S)-ethyl 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (200 mg, 1.04 mmol, Eq: 1.00) was added. After stirring overnight at rt, the reaction mixture was washed with saturated aqueous NaHCO3 (50 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 30% EtOAc in hexanes) to give (S)-ethyl 1-((S)-2-(tert-butoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (220 mg), m/z=434 (M+H).

Workup

  1. customto give a colorless solution
  2. stirringAfter stirring overnight at rt
  3. washthe reaction mixture was washed with saturated aqueous NaHCO3 (50 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 24 g, 0% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2efae8827ad14281b2a4ae4c46998071
Source dataset
uspto-grants-2016_04
Patent number
US09309248B2

Reaction notes

Loading…