Tetrahydrofuran → HCID 178445733, compound

HRID 2389100Notes

Reaction equation

HRID 2389100 reaction equation
[C:1]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([OH:11])[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].O[C:13]1[C:14]([C:30]([F:33])([F:32])[F:31])=[C:15]2[C:20](=[CH:21][CH:22]=1)[CH:19]=[C:18]([C@:23]1([CH3:29])[CH2:27][O:26][C:25](=[O:28])[NH:24]1)[CH:17]=[CH:16]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCC1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(Cl)Cl>[C:1]([C@H:5]1[CH2:6][CH2:7][C@H:8]([O:11][C:13]2[C:14]([C:30]([F:32])([F:33])[F:31])=[C:15]3[C:20](=[CH:21][CH:22]=2)[CH:19]=[C:18]([C@:23]2([CH3:29])[CH2:27][O:26][C:25](=[O:28])[NH:24]2)[CH:17]=[CH:16]3)[CH2:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 46196301(R)-4-(6-hydroxy-5-(trifluoromethyl)naphthalen-2-yl)-4-methyloxazolidin-2-oneHCID 178445811HCID 178445811, compound

Product 1

HCID 178445733HCID 178445733, compoundYield 30.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The mixture of cis-4-tert-butylcyclohexanol (30.4 mg, 0.000195 mol), (R)-4-(6-hydroxy-5-(trifluoromethyl)naphthalen-2-yl)-4-methyloxazolidin-2-one (50.5 mg, 0.000162 mol) and triphenylphosphine (51.1 mg, 0.000195 mol) in tetrahydrofuran (2 mL, 0.02 mol) was heated to reflux, and diisopropyl azodicarboxylate (0.0383 mL, 0.000195 mol) was added dropwise and was stirred and refluxed for 3 hours. The mixture was taken up into methylene chloride and subjected to chromatography purification with EtOAc/hexane (10:90 to 80:20) to give product (R)-4-(6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)-4-methyloxazolidin-2-one (22.2 mg, 30%). LCMS: Rf=2.41 min (450.46, M+1, 70%; 491.47, M+ACN, 100%). 1H NMR (400 MHz, CHLOROFORM-d) δ=8.25 (dd, J=8.7, 1.4 Hz, 1 H), 7.91 (d, J=9.0 Hz, 1 H), 7.79 (d, J=2.0 Hz, 1 H), 7.52 (dd, J=9.3, 2.3 Hz, 1 H), 7.34 (d, J=9.3 Hz, 1 H), 5.98 (br. s., 1 H), 4.45 (d, J=8.6 Hz, 1 H), 4.41 (d, J=8.6 Hz, 1 H), 4.38-4.26 (m, 1 H), 2.19 (d, J=13.1 Hz, 2 H), 1.89 (d, J=10.0 Hz, 2 H), 1.87 (s, 3 H), 1.59-1.48 (m, 2 H), 1.21-1.05 (m, 3 H), 0.89 (s, 9 H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperaturerefluxed for 3 hours
  4. customsubjected to chromatography purification with EtOAc/hexane (10:90 to 80:20)

Sources & evidence

ORD record
ord-8126cb3dd4c74a08ab14d753fc6cb327
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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