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

HRID 2389105Notes

Reaction equation

HRID 2389105 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, 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).

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-2ec799c3c4d64cf5b8bc444d04a71daf
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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