Ethanol → HCID 178464722, compound

HRID 2389053Notes

Reaction equation

HRID 2389053 reaction equation
[C:1]1([C@@H:7]2[CH2:12][CH2:11][C@H:10]([O:13][C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[CH:20]=[C:19]([C@:24]3([CH3:30])[CH2:28][O:27]C(=O)[NH:25]3)[CH:18]=[CH:17]4)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Li+].C(O)C.O>>[NH2:25][C@@:24]([C:19]1[CH:18]=[CH:17][C:16]2[C:21](=[CH:22][CH:23]=[C:14]([O:13][C@H:10]3[CH2:9][CH2:8][C@@H:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:12][CH2:11]3)[CH:15]=2)[CH:20]=1)([CH3:30])[CH2:28][OH:27]

Participants

5

Reactant 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 178421571HCID 178421571, compound

Product 1

HCID 178464722HCID 178464722, compoundYield 41.3%

Procedure

The mixture of (R)-4-(6-(cis-4-phenyl-cyclohexyloxy)naphthalen-2-yl)-4-methyloxazolidin-2-one (160 mg, 0.00040 mol) and lithium hydroxide (100 mg, 0.0044 mol) in ethanol (4 mL, 0.08 mol) and water (0.9 mL, 0.05 mol) was heated to reflux overnight. LCMS showed reaction complete. The solvent was removed under vacuum and the residue was partitioned between water and CH2Cl2. The aqueous layer was extensively extracted with CH2Cl2. The combined organic phase was dried over Na2SO4. The concentrated residue was taken up into DCM and subjected to chromatographic purification with CH2Cl2/MeOH (10:90 to 80:20) to give the product. A final purification on Gilson HPLC 0.1% TFA-ACN/H2O to gave the product as a white solid (62.0 mg, 41% yield). LCMS 359.33 ([M-NH2]+, 100%). 1H NMR (400 MHz, CD3OD) δ ppm 1.71 (brd, J=13.1 Hz, 2 H), 1.78 (s, 3 H), 1.83 (brd, J=14.7 Hz, 2 H), 1.98 (dd, J=13.7, 11.1 Hz, 2 H), 2.24 (d, J=12.6 Hz, 2 H), 2.67 (dd, J=11.6, 11.5 Hz, 1H), 3.82 (d, J=11.7 Hz, 1H), 3.92 (d, J=11.7 Hz, 1H), 4.84 (brs, 1H), 7.16 (m, 1H), 7.27-7.32 (m, 6H), 7.52 (d, J=8.7 Hz, 1H), 7.85 (m, 3H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customreaction complete
  4. customThe solvent was removed under vacuum
  5. customthe residue was partitioned between water and CH2Cl2
  6. extractionThe aqueous layer was extensively extracted with CH2Cl2
  7. dry with materialThe combined organic phase was dried over Na2SO4
  8. customsubjected to chromatographic purification with CH2Cl2/MeOH (10:90 to 80:20)
  9. customto give the product
  10. customA final purification on Gilson HPLC 0.1% TFA-ACN/H2O

Sources & evidence

ORD record
ord-22277077651041d995dcc2455606be8e
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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