Ethanol → (R)-2-amino-2-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)propan-1-ol

HRID 2389108Notes

Reaction equation

HRID 2389108 reaction equation
[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([CH2:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([C@:22]2([CH3:28])[CH2:26][O:25]C(=O)[NH:23]2)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+].C(O)C.O>>[NH2:23][C@@:22]([C:17]1[CH:16]=[CH:15][C:14]2[C:19](=[CH:20][CH:21]=[C:12]([CH2:11][CH:8]3[CH2:7][CH2:6][CH:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10][CH2:9]3)[CH:13]=2)[CH:18]=1)([CH3:28])[CH2:26][OH:25]

Participants

5

Reactant 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 67415438(R)-4-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)-4-methyloxazolidin-2-one

Product 1

HCID 46196282(R)-2-amino-2-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)propan-1-olYield 26.6%

Procedure

The mixture of (R)-4-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)-4-methyloxazolidin-2-one (18.6 mg, 0.0000490 mol) and lithium hydroxide (12.9 mg, 0.000539 mol) in ethanol (1 mL, 0.02 mol) and water (0.50 mL, 0.028 mol) was heated to reflux 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 with MeOH/CH2Cl2 (10:90 to 80:20) to give (R)-2-amino-2-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)propan-1-ol as a white solid (4.6 mg, 26%). LCMS: Rf=1.76 min 337.36 [M-NH2]+. 1H NMR (400 MHz, CHLOROFORM-d) δ=7.88 (s, 1 H), 7.77 (d, J=8.0 Hz, 1 H), 7.74 (d, J=7.0 Hz, 1 H), 7.56 (s, 1 H), 7.52 (dd, J=1.8, 8.7 Hz, 1 H), 7.32 (d, J=8.3 Hz, 1 H), 3.82-3.75 (m, 1 H), 3.72-3.67 (m, 1 H), 2.80 (d, J=8.0 Hz, 2 H), 2.69 (br. s., 1 H), 2.08 (br. s., 1 H), 1.64 (d, J=12.9 Hz, 2 H), 1.56 (br. s., 5 H), 1.46 (tt, J=4.0, 13.0 Hz, 2 H), 1.38-1.24 (m, 2 H), 1.03 (tt, J=3.1, 11.9 Hz, 1 H), 0.91 (s, 9 H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux 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 materialthe combined organic phase was dried over Na2SO4

Sources & evidence

ORD record
ord-5a090c1d85fb44d7960ae74cea76ea21
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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