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 747029ノート

反応式

HRID 747029 の反応式
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

参加物

6

反応物 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

生成物 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-ol収率 23%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒2 回

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-e3df77c3bda44df3b9cb52ec1b43b140
出典データセット
uspto-grants-2008_07
特許番号
US07393858B2

反応ノート

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