Ethanol → HCID 178464709, compound

HRID 2389055Notes

Reaction equation

HRID 2389055 reaction equation
[C:1]1([C@@H:7]2[CH2:12][CH2:11][C@H:10]([O:13][C:14]3[C:15]([C:31]([F:34])([F:33])[F:32])=[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)[C:15]=2[C:31]([F:33])([F:34])[F:32])[CH:20]=1)([CH3:30])[CH2:28][OH:27]

Participants

5

Reactant 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 178421566HCID 178421566, compound

Product 1

HCID 178464709HCID 178464709, compoundYield 50.1%

Procedure

The mixture of (R)-4-(6-(cis-4-phenyl-cyclohexyloxy)-5-trifluoromethylnaphthalen-2-yl)-4-methyloxazolidin-2-one (46.7 mg, 0.0000995 mol) and lithium hydroxide (26 mg, 0.0011 mol) in ethanol (2 mL, 0.04 mol) and water (0.4 mL, 0.02 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 as a white solid (22.1 mg, 50% yield). LCMS 427.26 ([M-NH2]+, 100%). 1H NMR (400 MHz, CD3OD) δ ppm 1.52 (s, 3 H), 1.67 (brd, J=11.8 Hz, 2 H), 1.82 (dd, J=13.4, 13.1 Hz, 2 H), 2.02 (ddd, J=13.1, 12.8, 3.0 Hz, 2 H), 2.20 (d, J=14.8 Hz, 2 H), 2.65 (ddd, J=12.2, 12.2, 3.8 Hz, 1H), 3.68 (d, J=10.9 Hz, 1H), 3.73 (d, J=10.9 Hz, 1H), 5.01 (brs, 1H), 7.14-7.30 (m, 5H), 7.50 (d, J=9.3 Hz, 1H), 7.71 (dd, J=9.3, 2.2 Hz, 1H), 7.95 (d, J=2.1 Hz, 1H), 8.08 (d, J=9.3 Hz, 1H), 8.16 (d, J=9.3 Hz, 1 H).

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)

Sources & evidence

ORD record
ord-913deccbede84988b6c7d3d92787c1c7
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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