Triethylamine → Rac-6-chloro-3-(3-chloro-benzyl)-3-[1-(morpholine-4-carbonyl)-piperidin-3-yl]-1,3-dihydro-indol-2-one

HRID 2102698Notes

Reaction equation

HRID 2102698 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)([CH:12]3[CH2:17][CH2:16][CH2:15][NH:14][CH2:13]3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[N:33]1([C:39](Cl)=[O:40])[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1>O1CCCC1>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)([CH:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:39]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)=[O:40])[CH2:13]3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 848104-Morpholinecarbonyl chlorideHCID 57803070Rac-6-chloro-3-(3-chloro-benzyl)-3-piperidin-3-yl-1,3-dihydro-indol-2-one

Product 1

HCID 11998151Rac-6-chloro-3-(3-chloro-benzyl)-3-[1-(morpholine-4-carbonyl)-piperidin-3-yl]-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of rac-6-chloro-3-(3-chloro-benzyl)-3-piperidin-3-yl-1,3-dihydro-indol-2-one (80 mg, 0.20 mmol) (from Example 25a supra) in tetrahydrofuran (3 mL) was added triethylamine (32 mg, 0.3 mmol), followed by the addition of morpholine-4-carbonyl chloride (38 mg, 0.24 mmol) (Aldrich). The mixture was stirred at 45° C. for 3 hours, then cooled to room temperature. The mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with another two portions of ethyl acetate. The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated. The residue were triturated with dichloromethane-hexanes to give rac-6-chloro-3-(3-chloro-benzyl)-3-[1-(morpholine-4-carbonyl)-piperidin-3-yl]-1,3-dihydro-indol-2-one as a white solid. (Yield 60 mg, 60%).

Workup

  1. temperaturecooled to room temperature
  2. customThe mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with another two portions of ethyl acetate
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue were triturated with dichloromethane-hexanes

Sources & evidence

ORD record
ord-7f6a5d7ca81c4be497208967edc90fda
Source dataset
uspto-grants-2009_08
Patent number
US07576082B2

Reaction notes

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