Ethanol → (2R)-2-amino-2-(6-(spiro[5.5]undecan-3-yloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol

HRID 2389105ノート

反応式

HRID 2389105 の反応式
[CH3:1][C@@:2]1([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:22][CH:23]4[CH2:28][CH2:27][C:26]5([CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]5)[CH2:25][CH2:24]4)[C:14]=3[C:18]([F:21])([F:20])[F:19])[CH:9]=2)[CH2:6][O:5]C(=O)[NH:3]1.[OH-].[Li+].C(O)C.O>>[NH2:3][C@@:2]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:22][CH:23]3[CH2:28][CH2:27][C:26]4([CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)[CH2:25][CH2:24]3)[C:14]=2[C:18]([F:20])([F:21])[F:19])[CH:9]=1)([CH3:1])[CH2:6][OH:5]

参加物

5

反応物 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 67413086(4R)-4-methyl-4-(6-(spiro[5.5]undecan-3-yloxy)-5-(trifluoromethyl)naphthalen-2-yl)oxazolidin-2-one

生成物 1

HCID 67414739(2R)-2-amino-2-(6-(spiro[5.5]undecan-3-yloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol収率 66.3%

実験手順

The mixture of (4R)-4-methyl-4-(6-(spiro[5.5]undecan-3-yloxy)-5-(trifluoromethyl)naphthalen-2-yl)oxazolidin-2-one (62.5 mg, 0.000135 mol) and lithium hydroxide (36 mg, 0.0015 mol) in ethanol (2 mL, 0.04 mol) and water (0.7 mL, 0.04 mol) was heated to reflux for overnight. The solvent was removed under vacuum and the residue was partitioned between water/CH2Cl2. The aqueous was extensively extracted with CH2Cl2. And the combined organic phase was dried over Na2SO4. The concentrated residue was taken up into methylene chloride and subjected to chromatography purification with MeOH/CH2Cl2 (10:90 to 80:20) to give (2R)-2-amino-2-(6-(spiro[5.5]undecan-3-yloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol as a white gel (39.0 mg, 66%). LCMS: Rf=1.86 min 419.30 ([M-16], 100%). 1H NMR (400 MHz, MeOD) δ=8.15 (dd, J=1.9, 9.2 Hz, 1 H), 8.07 (d, J=9.2 Hz, 1 H), 7.96 (d, J=2.1 Hz, 1 H), 7.71 (dd, J=2.2, 9.3 Hz, 1 H), 7.47 (d, J=9.3 Hz, 1 H), 4.68-4.59 (m, 1 H), 3.76 (d, J=10.8 Hz, 1 H), 3.70 (d, J=10.8 Hz, 1 H), 1.95-1.83 (m, 2 H), 1.82-1.67 (m, 4 H), 1.54 (s, 3 H), 1.53-1.42 (m, 8 H), 1.42-1.28 (m, 4 H).

後処理

  1. temperaturewas heated
  2. temperatureto reflux for overnight
  3. customThe solvent was removed under vacuum
  4. customthe residue was partitioned between water/CH2Cl2
  5. extractionThe aqueous was extensively extracted with CH2Cl2
  6. dry with materialAnd the combined organic phase was dried over Na2SO4
  7. customsubjected to chromatography purification with MeOH/CH2Cl2 (10:90 to 80:20)

出典と根拠

ORDレコード
ord-2ec799c3c4d64cf5b8bc444d04a71daf
出典データセット
uspto-grants-2012_09
特許番号
US08269043B2

反応ノート

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