Acetonitrile → (4RS)-8-[(2R,3R,4R)-2-[(1R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(3,4-difluorophenyl)-tetrahydropyran-4-yl]methyl-2-oxa-8-aza-spiro[4.5]decan-4-ol

HRID 747031Notes

Reaction equation

HRID 747031 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:21]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[C:24]([F:29])[CH:23]=3)[C@H:20]([CH2:30]OS(C)(=O)=O)[CH2:19][CH2:18][O:17]2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.[CH2:39]1[C:43]2([CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH:42]([OH:49])[CH2:41][O:40]1.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O>[F:1][C:2]([F:36])([F:37])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:21]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[C:24]([F:29])[CH:23]=3)[C@H:20]([CH2:30][N:46]3[CH2:45][CH2:44][C:43]4([CH2:39][O:40][CH2:41][CH:42]4[OH:49])[CH2:48][CH2:47]3)[CH2:19][CH2:18][O:17]2)[CH3:14])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 219553632-Oxa-8-azaspiro[4.5]decan-4-ol;hydrochlorideHCID 86606915Methanesulfonic acid [(2R,3R,4R)-2-[(1R)-1-(3,5-Bis(trifluoromethyl)-phenyl)ethoxy]-3-(3,4-difluorophenyl)-tetrahydropyran-4-yl]methyl ester

Product 1

HCID 86606924(4RS)-8-[(2R,3R,4R)-2-[(1R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(3,4-difluorophenyl)-tetrahydropyran-4-yl]methyl-2-oxa-8-aza-spiro[4.5]decan-4-ol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of methanesulfonic acid [(2R,3R,4R)-2-[(1R)-1-(3,5-bis(trifluoromethyl)-phenyl)ethoxy]-3-(3,4-difluorophenyl)-tetrahydropyran-4-yl]methyl ester (Description 16; 0.275 g, 0.49 mmol), 2-oxa-8-aza-spiro[4.5]decan-4-ol hydrochloride (Description 8; 0.1 g, 0.37 mmol), potassium carbonate (237 g, 1.7 mmol) and acetonitrile (3 ml) was stirred at 55° C. overnight and then at 65° C. for 18 hours. The mixture was treated with water and extracted into dichloromethane. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by preparative TLC (dichloromethane:methanol) to give the title compound.

Workup

  1. waitat 65° C. for 18 hours
  2. extractionextracted into dichloromethane
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by preparative TLC (dichloromethane:methanol)

Sources & evidence

ORD record
ord-be07b4c6d92e470f875b1ca727dee5e3
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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