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

HRID 1036442Notes

Reaction equation

HRID 1036442 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:18][CH:19]4[CH2:24][CH2:23][C:22]5([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]5)[CH2:21][CH2:20]4)[CH:14]=3)[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:18][CH:19]3[CH2:24][CH2:23][C:22]4([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]4)[CH2:21][CH2:20]3)[CH:14]=2)[CH:9]=1)([CH3:1])[CH2:6][OH:5]

Participants

5

Reactant 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 67414094(4R)-4-methyl-4-(6-(spiro[5.5]undecan-3-yloxy)naphthalen-2-yl)oxazolidin-2-one

Product 1

HCID 67415580(2R)-2-amino-2-(6-(spiro[5.5]undecan-3-yloxy)naphthalen-2-yl)propan-1-olYield 31.2%

Procedure

The mixture of (4R)-4-methyl-4-(6-(spiro[5.5]undecan-3-yloxy)naphthalen-2-yl)oxazolidin-2-one (324 mg, 0.000823 mol) and lithium hydroxide (294 mg, 0.0123 mol) in ethanol (7.1 mL, 0.12 mol) and water (2.4 mL, 0.13 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 the product (2R)-2-amino-2-(6-(spiro[5.5]undecan-3-yloxy)naphthalen-2-yl)propan-1-ol as a white powder (94.5 mg, 31.2%). LCMS Rf=1.70 min 351.34 ([M−NH2]+, 100%). 1H NMR (400 MHz, MeOD) δ=7.86 (d, J=1.6 Hz, 1H), 7.78 (d, J=9.0 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.57 (dd, J=2.0, 8.7 Hz, 1H), 7.22 (d, J=2.1 Hz, 1H), 7.14 (dd, J=2.4, 8.9 Hz, 1H), 4.53-4.44 (m, 1H), 3.75 (d, J=11.0 Hz, 1H), 3.70 (d, J=11.0 Hz, 1H), 2.01-1.88 (m, 2H), 1.80-1.65 (m, 4H), 1.55 (s, 3H), 1.50 (m, 8H), 1.42-1.30 (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 materialthe 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-fe7bc15238c74e7bbf3521cfe0c6ec7b
Source dataset
uspto-grants-2013_10
Patent number
US08546359B2

Reaction notes

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