Triethylamine → Tert-butyl 3-{[(2-chloro-3,6-difluorobenzoyl)amino]methyl}-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate

HRID 2100312Notes

Reaction equation

HRID 2100312 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]([F:12])[C:3]=1[C:4](Cl)=[O:5].[NH2:13][CH2:14][C:15]1([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][N:27]2[CH3:32])[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]([F:12])[C:3]=1[C:4]([NH:13][CH2:14][C:15]1([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][N:27]2[CH3:32])[CH2:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18]1)=[O:5]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27735362-Chloro-3,6-difluorobenzoyl chlorideHCID 57798322Tert-butyl 3-(aminomethyl)-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate

Product 1

HCID 57798318Tert-butyl 3-{[(2-chloro-3,6-difluorobenzoyl)amino]methyl}-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-chloro-3,6-difluorobenzoyl chloride (0.38 ml, 2.7 mmol) was added to tert-butyl 3-(aminomethyl)-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate (0.55 g, 1.9 mmol) in dichloromethane (6 ml) and triethylamine (0.54 ml, 3.9 mmol) at 0° C. The reaction was stirred at 0° C. for 15 mins, before warming to room temperature. After 30 mins, lc-ms showed complete consumption of starting material. The reaction was quenched and the resulting mixture was partitioned between dichloromethane and water. The organic phase was washed with brine, dried over anhydrous magnesium sulfate and evaporated to dryness. Purification by flash column chromatography on silica gel eluting with dichloromethane (containing 1% ammonia) on a gradient of methanol (0-8%) led to tert-butyl 3-{[(2-chloro-3,6-difluorobenzoyl)amino]methyl}-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate as a white solid. m/z (M++H) 458.

Workup

  1. temperaturebefore warming to room temperature
  2. waitAfter 30 mins
  3. customconsumption of starting material
  4. customThe reaction was quenched
  5. customthe resulting mixture was partitioned between dichloromethane and water
  6. washThe organic phase was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customevaporated to dryness
  9. customPurification by flash column chromatography on silica gel eluting with dichloromethane (containing 1% ammonia) on a gradient of methanol (0-8%)

Sources & evidence

ORD record
ord-79312b631ed346d3bd9ab089ef653735
Source dataset
uspto-grants-2009_08
Patent number
US07572792B2

Reaction notes

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