Dichloromethane → Tert-butyl 4-hydroxy-4-{[(3-nitro[1,5]naphthyridin-4-yl)amino]methyl}piperidine-1-carboxylate

HRID 1469314Notes

Reaction equation

HRID 1469314 reaction equation
[NH2:1][CH2:2][C:3]1([OH:16])[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.C([N:19]([CH2:22][CH3:23])[CH2:20][CH3:21])C.Cl[C:25]1C2C(=NC=CC=2)[N:28]=[CH:27][C:26]=1[N+:35]([O-:37])=[O:36].Cl[CH2:39]Cl>C(=O)(O)[O-].[Na+]>[OH:16][C:3]1([CH2:2][NH:1][C:25]2[C:20]3[C:21](=[CH:39][CH:23]=[CH:22][N:19]=3)[N:28]=[CH:27][C:26]=2[N+:35]([O-:37])=[O:36])[CH2:4][CH2:5][N:6]([C:9]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:10])[CH2:7][CH2:8]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 125432134-Chloro-3-nitronaphthyridineHCID 23396319tert-Butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 57515527Tert-butyl 4-hydroxy-4-{[(3-nitro[1,5]naphthyridin-4-yl)amino]methyl}piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Under a nitrogen atmosphere a solution of tert-butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate (38.9 g, 169 mmol, prepared according to Parts A and B of Example 4) in dichloromethane (420 mL) was cooled to 0° C. Triethylamine (23.6 mL, 169 mmol) was added followed by the portionwise addition of 4-chloro-3-nitronaphthyridine (30.8 g, 147 mmol). The reaction mixture was stirred at ambient temperature overnight and then diluted with saturated aqueous sodium bicarbonate (200 mL). The layers were separated and the aqueous was extracted with dichloromethane (3×100 mL). The combined organics were concentrated under reduced pressure to provide a dark yellow solid. This material was triturated with saturated aqueous sodium bicarbonate, isolated by filtration, rinsed well with water, and then dried in a vacuum oven at 70° C. overnight to provide 58.85 g of tert-butyl 4-hydroxy-4-{[(3-nitro[1,5]naphthyridin-4-yl)amino]methyl}piperidine-1-carboxylate as a yellow solid.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous was extracted with dichloromethane (3×100 mL)
  3. concentrationThe combined organics were concentrated under reduced pressure
  4. customto provide a dark yellow solid
  5. customThis material was triturated with saturated aqueous sodium bicarbonate
  6. customisolated by filtration
  7. washrinsed well with water
  8. customdried in a vacuum oven at 70° C. overnight

Sources & evidence

ORD record
ord-5af54a179495455c96fb5499e47e2e9a
Source dataset
uspto-grants-2015_04
Patent number
US09006264B2

Reaction notes

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