Sodium Carbonate → HCID 86674691, compound

HRID 571839Notes

Reaction equation

HRID 571839 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][C:3]=1[CH3:21].[C:22](=[O:25])([O-])[O-].[Na+].[Na+].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[Cl:40][C:41]1[N:46]=[CH:45][C:44]([NH2:47])=[CH:43][CH:42]=1>ClCCl.O>[Cl:40][C:41]1[N:46]=[CH:45][C:44]([NH:47][C:22](=[O:25])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([C@H:8]3[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:9]3)=[CH:4][C:3]=2[CH3:21])=[CH:43][CH:42]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 793055-Amino-2-chloropyridineHCID 94429TriphosgeneHCID 68325701HCID 68325701, compound

Product 1

HCID 86674691HCID 86674691, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (+)-(R)-tert-butyl 2-(4-amino-3-methylphenyl)morpholine-4-carboxylate (99 mg) in dichloromethane (3 ml) was added a solution of sodium carbonate (72 mg) in water (3 ml). The reaction mixture was cooled to 0° C. and triphosgene (37 mg) was added. The reaction mixture was then stirred at 0° C. for 1 hour. TLC showed all the starting material had reacted. 6-Chloropyridin-3-amine (48 mg, CAS 5350-93-6) was then added and the reaction mixture was stirred at room temperature for a further hour. TLC showed the reaction was complete. The reaction mixture was poured into dichloromethane and extracted with water. The organic phase was separated, dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: 0% to 70% EtOAc in hexanes) to give (R)-tert-butyl 2-(4-(3-(6-chloropyridin-3-yl)ureido)-3-methylphenyl)morpholine-4-carboxylate (106 mg, 70%) as an off-white solid. MS (ISP): 449.2 ([{37Cl}M+H]+), 447.2 ([{35Cl}M+H]+).

Workup

  1. customhad reacted
  2. stirringthe reaction mixture was stirred at room temperature for a further hour
  3. extractionextracted with water
  4. customThe organic phase was separated
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2; gradient: 0% to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d569b26cfa794cecb7cd4d081d7f2cf6
Source dataset
uspto-grants-2015_05
Patent number
US09029370B2

Reaction notes

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