Potassium Iodide → HCID 131726487, compound

HRID 1765994Notes

Reaction equation

HRID 1765994 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1)=[O:7].[I-].[K+].[ClH:34].[Cl:35][CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][O:41][C@H:40]([CH2:44][O:45][CH3:46])[CH2:39]1.C(N(CC)C(C)C)(C)C>O.C(OCC)(=O)C.CN(C)C=O>[OH2:7].[ClH:35].[ClH:34].[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:36][CH2:37][N:38]2[CH2:43][CH2:42][O:41][C@H:40]([CH2:44][O:45][CH3:46])[CH2:39]2)[CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1)=[O:7].[OH2:7].[OH2:7].[F:31][C:2]([C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:36][CH2:37][N:38]2[CH2:43][CH2:42][O:41][C@H:40]([CH2:44][O:45][CH3:46])[CH2:39]2)[CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([OH:22])[CH:16]=1)=[O:7])([F:1])[F:30].[ClH:35].[ClH:35]

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 11236182HCID 11236182, compoundHCID 69331371HCID 69331371, compound

Product 1

HCID 131726487HCID 131726487, compoundYield 191.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
52.5 °C

Procedure

Into N,N-dimethylformamide (33.5 ml) were charged (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3-hydroxy-4-methylbenzyl)piperazine (6.7 g), potassium iodide (8.0 g), (2S)-4-(2-chloroethyl)-2-(methoxymethyl)morpholine hydrochloride (4.3 g) and N,N-diisopropylethylamine (4.8 g). The temperature was raised to 50 to 55° C. and allowed to react for 5 hours. After the reaction was completed, the reaction solution was cooled to room temperature. Ethyl acetate (33.5 ml) and water (33.5 ml) were added and mixed. After mixing was completed, layers were separated. The organic layer was washed by adding water (33.5 ml), layers were separated and the organic layer was concentrated. Ethyl acetate (33.5 ml) was added to the obtained oil of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[2-[(2S)-2-(methoxymethyl)-morpholino]ethyl]-2-(3-hydroxy-4-methylbenzyl)piperazine to effect dissolution and then the solution was concentrated. The obtained concentrate was diluted with acetone (100 ml), clarified and filtered, and washed with acetone (34 ml). Concentrated hydrochloric acid (3.9 g) was added dropwise to the combined filtrate and washings at room temperature and crystallization was effected under ice-cooling for 8 hours. Crystals were collected by filtration, washed with acetone (33.5 ml), dried under reduced pressure and moistured to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]-2-(3-hydroxy-4-methyl-benzyl)piperazine dihydrochloride sesquihydrate (8.1 g, yield: 76.7%) in the form of white crystals.

Workup

  1. customto react for 5 hours
  2. temperaturethe reaction solution was cooled to room temperature
  3. additionmixed
  4. additionAfter mixing
  5. customlayers were separated
  6. washThe organic layer was washed
  7. additionby adding water (33.5 ml), layers
  8. customwere separated
  9. concentrationthe organic layer was concentrated
  10. additionEthyl acetate (33.5 ml) was added to the obtained oil of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[2-[(2S)-2-(methoxymethyl)-morpholino]ethyl]-2-(3-hydroxy-4-methylbenzyl)piperazine
  11. dissolutiondissolution
  12. concentrationthe solution was concentrated
  13. concentrationThe obtained concentrate
  14. additionwas diluted with acetone (100 ml)
  15. filtrationfiltered
  16. washwashed with acetone (34 ml)
  17. additionConcentrated hydrochloric acid (3.9 g) was added dropwise to the combined filtrate and washings at room temperature
  18. customcrystallization
  19. temperaturecooling for 8 hours
  20. filtrationCrystals were collected by filtration
  21. washwashed with acetone (33.5 ml)
  22. customdried under reduced pressure

Sources & evidence

ORD record
ord-c980fd092f8a44f3ad2da11fa8584d5f
Source dataset
uspto-grants-2007_06
Patent number
US07229992B2

Reaction notes

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