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

HRID 747029Notes

Reaction equation

HRID 747029 reaction equation
C(N(CC)CC)C.Cl.[CH2:9]1[C:13]2([CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH:12]([OH:19])[CH2:11][O:10]1.[F:20][C:21]([F:50])([F:49])[C:22]1[CH:23]=[C:24]([C@H:32]([O:34][C@@H:35]2[C@@H:40]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C@H:39]([CH:47]=O)[CH2:38][CH2:37][O:36]2)[CH3:33])[CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:30][C:28]([F:29])([F:31])[C:26]1[CH:25]=[C:24]([C@H:32]([O:34][C@@H:35]2[C@@H:40]([C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C@H:39]([CH2:47][N:16]3[CH2:17][CH2:18][C:13]4([CH2:9][O:10][CH2:11][CH:12]4[OH:19])[CH2:14][CH2:15]3)[CH2:38][CH2:37][O:36]2)[CH3:33])[CH:23]=[C:22]([C:21]([F:50])([F:49])[F:20])[CH:27]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 219553632-Oxa-8-azaspiro[4.5]decan-4-ol;hydrochlorideHCID 86601738(2R,3R,4R)-2-[(1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy]-3-phenyl-tetrahydropyran-4-carbaldehyde

Product 1

HCID 86606923(4RS)-8-[(2R,3R,4R)-2-[(1R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-phenyl-tetrahydropyran-4-yl]methyl-2-oxa-8-aza-spiro[4.5]decan-4-olYield 23%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

Triethylamine (140 μL, 1.0 mmol) was added to a suspension of 2-oxa-8-aza-spiro[4.5]decan-4-ol hydrochloride (Description 8; 0.1 g, 0.54 mmol) in 1,2-dichloroethane (2 ml). After 10 minutes, (2R,3R,4R)-2-[(1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy]-3-phenyl-tetrahydropyran-4-carbaldehyde (see Example 43 in WO 00/56727; 0.24 g, 0.54 mmol) was added as a solution in 1,2-dichloroethane (3 ml). The mixture was stirred at room temperature for 30 minutes then sodium triacetoxyborohydride (0.2 g, 0.94 mmol) was added. The reaction was stirred at room temperature overnight. The mixture was partitioned between dichloromethane and brine. The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was purified by preparative thin layer chromatography, eluting with 5% methanol/dichloromethane, to give the title compound (72 mg, 23%).

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. customThe mixture was partitioned between dichloromethane and brine
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative thin layer chromatography
  6. washeluting with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-e3df77c3bda44df3b9cb52ec1b43b140
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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