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

HRID 1036445Notes

Reaction equation

HRID 1036445 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Procedure

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, 1H), 8.07 (d, J=9.2 Hz, 1H), 7.96 (d, J=2.1 Hz, 1H), 7.71 (dd, J=2.2, 9.3 Hz, 1H), 7.47 (d, J=9.3 Hz, 1H), 4.68-4.59 (m, 1H), 3.76 (d, J=10.8 Hz, 1H), 3.70 (d, J=10.8 Hz, 1H), 1.95-1.83 (m, 2H), 1.82-1.67 (m, 4H), 1.54 (s, 3H), 1.53-1.42 (m, 8H), 1.42-1.28 (m, 4H).

Workup

  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)

Sources & evidence

ORD record
ord-00d47ac1c0804f29a6c86d275c182a24
Source dataset
uspto-grants-2013_10
Patent number
US08546359B2

Reaction notes

Loading…