Ammonium Chloride → HCID 86674236, compound

HRID 1909097Notes

Reaction equation

HRID 1909097 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([O:6][CH2:7][C@:8]([CH3:12])([OH:11])[CH2:9][OH:10])=[CH:4][CH:3]=1.[F:15][C:16]([F:32])([F:31])[O:17][C:18]1[CH:30]=[CH:29][C:21]([O:22][CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[CH:20][CH:19]=1.CC(C)([O-])C.[Na+].[Cl-].[NH4+].O.[C:42]1([CH3:52])[CH:47]=[CH:46][C:45]([S:48]([OH:51])(=[O:50])=[O:49])=[CH:44][CH:43]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C1(C)C=CC=CC=1>[C:42]1([CH3:52])[CH:43]=[CH:44][C:45]([S:48]([OH:51])(=[O:49])=[O:50])=[CH:46][CH:47]=1.[CH3:12][C@:8]([OH:11])([CH2:7][O:6][C:5]1[CH:13]=[CH:14][C:2]([N:26]2[CH2:27][CH2:28][CH:23]([O:22][C:21]3[CH:20]=[CH:19][C:18]([O:17][C:16]([F:15])([F:31])[F:32])=[CH:30][CH:29]=3)[CH2:24][CH2:25]2)=[CH:3][CH:4]=1)[CH2:9][OH:10]

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 161154394-[4-(Trifluoromethoxy)phenoxy]piperidineHCID 23676156Sodium t-butoxideHCID 71059491HCID 71059491, compound

Product 1

HCID 86674236HCID 86674236, compoundYield 85.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

(R)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diol (20.0 kg, 76.6 mol), 4-[4-(trifluoromethoxy)phenoxy]piperidine (22.0 kg, 84.3 mol), tris(dibenzylideneacetone)dipalladium (0) (175 g, 0.19 mol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (195 g, 0.46 mol), sodium tert-butoxide (8.46 kg, 88.0 mol), and toluene (240 ml) were mixed, followed by stirring under an argon atmosphere at 70° C. for 3 hours. After cooling, an ammonium chloride aqueous solution was added to the reaction mixture, followed by extraction with toluene. Isopropanol was flowed therein, and p-toluenesulfonic acid monohydrate (16.0 kg, 84.1 mol) was added thereto, followed by stirring. The precipitated crystals thus obtained were collected by filtration and dried, obtaining 40.3 kg of (R)-2-methyl-3-(4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenoxy)propane-1,2-diol p-toluenesulfonic acid salt (yield: 85.7%).

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with toluene
  3. stirringby stirring
  4. customThe precipitated crystals thus obtained
  5. filtrationwere collected by filtration
  6. customdried

Sources & evidence

ORD record
ord-d8063b5e244646699340c273c205d66d
Source dataset
uspto-grants-2013_12
Patent number
US08598358B2

Reaction notes

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