Dimethylformamide → Ethyl 2-{4-[(2-methylpropyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate

HRID 1777303Notes

Reaction equation

HRID 1777303 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:22][CH2:21][C:8]2([CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][CH:15]([C:18](O)=[O:19])[CH2:14][CH2:13]3)[CH2:9]2)[CH2:7]1)=[O:5])[CH3:2].C[N:24]([CH:26]=O)C.CN(C(ON1N=N[C:38]2[CH:39]=CC=N[C:37]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>>[CH3:37][CH:38]([CH3:39])[CH2:26][NH:24][C:18]([CH:15]1[CH2:14][CH2:13][N:12]([CH:10]2[CH2:9][C:8]3([CH2:21][CH2:22][N:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7]3)[CH2:11]2)[CH2:17][CH2:16]1)=[O:19]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 900796681-[6-(Ethoxycarbonyl)-6-azaspiro[3.4]oct-2-yl]piperidine-4-carboxylic acid

Product 1

HCID 73438536Ethyl 2-{4-[(2-methylpropyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylateYield 37.7%

Procedure

1-[6-(Ethoxycarbonyl)-6-azaspiro[3.4]oct-2-yl]piperidine-4-carboxylic acid (0.200 g, 0.65 mmol) was dissolved in DMF (5 mL) isobutylamine (0.071 g, 0.97 mmol), HATU (0.270 g, 0.71 mmol) and DIPEA (0.417 g, 3.23 mmol) were added. The reaction mixture was stirred at rt overnight under nitrogen. The solvents were removed in vacuo, and the residue was partitioned between DCM and sat. NaHCO3 sol., organic layer washed with sat. NaCl sol. and dried over MgSO4. The solvents were removed in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 A, 12 mL per min, gradient 0% to 10% MeOH in DCM]) to give ethyl 2-{4-[(2-methylpropyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate (0.089 g, 37.7%) as a pale yellow gum as a mixture of diastereomers.

Workup

  1. customThe solvents were removed in vacuo
  2. customthe residue was partitioned between DCM and sat. NaHCO3 sol., organic layer
  3. washwashed with sat. NaCl sol.
  4. dry with materialdried over MgSO4
  5. customThe solvents were removed in vacuo
  6. customthe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 A, 12 mL per min, gradient 0% to 10% MeOH in DCM])

Sources & evidence

ORD record
ord-33cc9767f0a346018e25aa28ffada92f
Source dataset
uspto-grants-2016_02
Patent number
US09266857B2

Reaction notes

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