Toluene → Tert-butyl 2,2-dimethyl-5-(5-(trifluoromethyl)-6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)-1,3-dioxan-5-ylcarbamate

HRID 2389094Notes

Reaction equation

HRID 2389094 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[C:21]([OH:30])[C:22]=3[C:26]([F:29])([F:28])[F:27])[CH:17]=2)[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[O:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:32][C:33]([F:42])([F:41])[CH:34]1[CH2:39][CH2:38][CH:37](O)[CH2:36][CH2:35]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[CH3:14][C:11]1([CH3:15])[O:12][CH2:13][C:8]([NH:7][C:6](=[O:31])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[C:21]([O:30][CH:37]4[CH2:38][CH2:39][CH:34]([C:33]([F:42])([F:41])[F:32])[CH2:35][CH2:36]4)[C:22]=3[C:26]([F:27])([F:28])[F:29])[CH:17]=2)[CH2:9][O:10]1

Participants

8

Reactant 6

HCID 1140TolueneHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 27797654-(Trifluoromethyl)cyclohexan-1-olHCID 5363146Diisopropyl azodicarboxylateHCID 67412806tert-Butyl 5-(6-hydroxy-5-(trifluoromethyl)naphthalen-2-yl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamate

Product 1

HCID 86642890Tert-butyl 2,2-dimethyl-5-(5-(trifluoromethyl)-6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)-1,3-dioxan-5-ylcarbamateYield 64.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

[5-(6-Hydroxy-5-trifluoromethyl-naphthalen-2-yl)-2,2-dimethyl-1,3-dioxinan-5-yl]-carbamic acid tert-butyl ester (1 g, 0.003 mol), 4-Trifluoromethyl-cyclohexanol (0.50 g, 0.0029 mol), and triphenylphosphine (0.84 g, 0.0032 mol) were combined in dry toluene (15 mL, 0.14 mol) and stirred under nitrogen. The solution cooled to 0° C. on an ice bath and diisopropyl azodicarboxylate (0.65 g, 0.0032 mol) was added slowly (dropwise) over 30 min. Once all DIAD was added the mixture was stirred on an icebath for 30 minutes. The ice bath was then removed and the mixture was allowed to warm to room temperature while stirring under nitrogen for 16 hours. The mixture was then washed with 1.0 N HCl, and washed with Sat. Na2CO3, and brine. The organic layer was dried over MgSO4, filtered, and concentrated to dryness under reduced pressure. The crude reaction was then dissolved in methylene chloride, absorbed onto 10 g silica and purified (dry load) via column chromatography 0-50% EtoAC/Hexanes using a 125 g column to give 1.1 g the desired product as a white solid. Material was carried forward without additional purification. ESI-MS: 592 (M+H)+

Workup

  1. stirringwas stirred on an icebath for 30 minutes
  2. customThe ice bath was then removed
  3. temperatureto warm to room temperature
  4. stirringwhile stirring under nitrogen for 16 hours
  5. washThe mixture was then washed with 1.0 N HCl
  6. washwashed with Sat. Na2CO3, and brine
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe crude reaction
  11. customabsorbed onto 10 g silica
  12. custompurified
  13. dry with material(dry load) via column chromatography 0-50% EtoAC/Hexanes using a 125 g column

Sources & evidence

ORD record
ord-b8e68e305bcc4c7b97372da1305cf249
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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