Ammonium Chloride → 1,2-Propanediol, 2-methyl-3-[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl]phenoxy]-, (2R)-

HRID 1909090Notes

Reaction equation

HRID 1909090 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.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.CC(C)([O-])C.[Na+].[Cl-].[NH4+]>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].C1(C)C=CC=CC=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

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 161154394-[4-(Trifluoromethoxy)phenoxy]piperidineHCID 23676156Sodium t-butoxideHCID 71059491HCID 71059491, compound

Product 1

HCID 673594871,2-Propanediol, 2-methyl-3-[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl]phenoxy]-, (2R)-

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

(R)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diol (87.96 g, 336.9 mmol, optical purity of 92.2% ee), 4-[4-(trifluoromethoxy)phenoxy]piperidine (80 g, 306.2 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2dba3, 701 mg, 0.77 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (780 mg, 1.84 mmol), sodium tert-butoxide (33.85 g, 352.2 mmol), and toluene (240 ml) were mixed, followed by stirring under an argon atmosphere at 70° C. for 6 hours. After cooling, an ammonium chloride aqueous solution was added to the reaction mixture, followed by extraction with toluene. Thereafter, the organic layer was distilled off under reduced pressure, obtaining a crude product of (R)-2-methyl-3-(4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenoxy)propane-1,2-diol.

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with toluene
  3. distillationThereafter, the organic layer was distilled off under reduced pressure

Sources & evidence

ORD record
ord-f62a7c4215754ec19c75d9fb80c786f9
Source dataset
uspto-grants-2013_12
Patent number
US08598358B2

Reaction notes

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