Ethanol → HCID 178464709, compound

HRID 1036395Notes

Reaction equation

HRID 1036395 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, 3H), 1.67 (brd, J=11.8 Hz, 2H), 1.82 (dd, J=13.4, 13.1 Hz, 2H), 2.02 (ddd, J=13.1, 12.8, 3.0 Hz, 2H), 2.20 (d, J=14.8 Hz, 2H), 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, 1H).

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-cfd6793c59b64cd3be7e2c851010f4da
Source dataset
uspto-grants-2013_10
Patent number
US08546359B2

Reaction notes

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