Acetic Acid → tert-Butyl 7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane-2-carboxylate

HRID 1913448Notes

Reaction equation

HRID 1913448 reaction equation
Cl.[CH2:2]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[CH2:4][N:3]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C([N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])C.[C:25]([OH:28])(=O)[CH3:26].CN([C:32]([O:36]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl[CH2:54]Cl>>[CH3:32][O:36][C:22]1[CH:54]=[CH:24][C:23]([CH2:26][C:25]([N:8]2[CH2:7][CH2:6][C:5]3([CH2:4][N:3]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:2]3)[CH2:10][CH2:9]2)=[O:28])=[N:20][CH:21]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 24820549tert-Butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate hydrochloride

Product 1

HCID 58438449tert-Butyl 7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane-2-carboxylateYield 96%

Procedure

In an oven dried round-bottomed flask was suspended tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate hydrochloride (1.89 g, 7.18 mmol) in anhydrous dichloromethane (50 mL). Triethylamine (2 mL, 14.4 mmol) followed by 5-methoxypyridin-2-yl)acetic acid (SM-1aa, 1.2 g, 7.18 mmol) were added. HATU (3.28 g, 8.62 mmol) was added and the resulting bright yellow solution was stirred at room temperature for 15 hours. The reaction mixture was washed consecutively with saturated aqueous sodium bicarbonate, water and brine and was dried over anhydrous MgSO4. Filtration and solvent removal afforded the crude material as a brownish oil (4.8 g). The product was purified by silica chromatography using a Combiflash ISCO (Teledyne Isco Inc., Lincoln, Nebr.) system to give the title compound (2-1a) as a light yellow foam (2.57 g, 96%). MS (ES+) 376.4 (M+H)+. 1H NMR (CDCl3) δ 1.42 (s, 9H), 1.57-1.61 (m, 2H), 1.65-1.69 (m, 2H), 3.47-3.54 (m, 4H), 3.58-3.64 (m, 4H), 3.83 (s, 3H), 3.85 (s, 2H), 7.15-7.18 (m, 1H), 7.23-7.26 (m, 1H), 8.18 (d, 1H).

Workup

  1. customIn an oven dried round-bottomed flask was suspended
  2. additionwere added
  3. washThe reaction mixture was washed consecutively with saturated aqueous sodium bicarbonate, water and brine
  4. dry with materialwas dried over anhydrous MgSO4
  5. filtrationFiltration and solvent removal
  6. customafforded the crude material as a brownish oil (4.8 g)
  7. customThe product was purified by silica chromatography

Sources & evidence

ORD record
ord-af08487eb50c404f843080a2cfb984a0
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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