Benzaldehyde → HCID 178477573, compound

HRID 853125Notes

Reaction equation

HRID 853125 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])[CH2:4][CH2:3]1.CCN(CC)CC.[CH:25](=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1CCN2C(=NCCC2)CC1.[Si:44](Cl)([CH2:49][CH3:50])([CH2:47][CH3:48])[CH2:45][CH3:46].[NH4+].[Cl-].[BH4-].[Na+]>C(O)C.CN(C=O)C.CCOCC>[CH2:25]([NH:1][C@H:2]1[CH2:3][CH2:4][C@@H:5]([C:8]([O:17][Si:44]([CH2:49][CH3:50])([CH2:47][CH3:48])[CH2:45][CH3:46])([C:13]([F:14])([F:15])[F:16])[C:9]([F:11])([F:12])[F:10])[CH2:6][CH2:7]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[CH2:25]([NH:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([C:8]([O:17][Si:44]([CH2:49][CH3:50])([CH2:47][CH3:48])[CH2:45][CH3:46])([C:13]([F:14])([F:15])[F:16])[C:9]([F:11])([F:12])[F:10])[CH2:6][CH2:7]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

12

Reactant 7

HCID 240BenzaldehydeHCID 8471TriethylamineHCID 13819ChlorotriethylsilaneHCID 25517Ammonium ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 4311764Sodium borohydrideHCID 86605616HCID 86605616, compound

Product 2

HCID 178477572HCID 178477572, compoundYield 14%HCID 178477573HCID 178477573, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 17 g (78.23 mmol) of the acetate salt of 2-(4-amino-cyclohexyl)-1,1,1,3,3,3-hexafluoro-propan-2-ol (example 2.1) in 250 mL of ethanol was treated with 27.2 mL (196 mmol) of NEt3 and 8.75 mL (86.1 mmol) of benzaldehyde. The mixture was stirred overnight at RT and the solvents evaporated i.v. The brown oil obtained was dissolved in 120 mL of DMF and treated with 8.76 mL (58.7 mmol) of DBU and then dropwise with 9.85 mL (58.7 mmol) of TESCl. The mixture was stirred for 4 hrs at RT and distributed between a saturated aqueous solution of NH4Cl and Et2O. The crude material obtained after drying of the combined organic phases over Na2SO4 and evaporation of the solvent was dissolved in 250 mL of ethanol and treated portionwise with 2.2 g (58.7 mmol) of NaBH4 and stirred for 2 hrs at RT. Evaporation of the solvent, distribution between Et2O and an aqueous solution of NaOH, drying of the combined organic phases over Na2SO4 and chromatography on silica gel with heptane/EtOAc (gradient from 6:1 to 2:1) yielded 3.3 g (14%) of cis benzyl-[4-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-cyclohexyl]-amine and 4.7 g (20%) trans benzyl-[4-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-cyclohexyl]-amine as a yellow oil, MS: 470 (M+H)+.

Workup

  1. customthe solvents evaporated i.v
  2. customThe brown oil obtained
  3. stirringThe mixture was stirred for 4 hrs at RT
  4. customThe crude material obtained
  5. dry with materialafter drying of the combined organic phases over Na2SO4 and evaporation of the solvent
  6. dissolutionwas dissolved in 250 mL of ethanol
  7. stirringstirred for 2 hrs at RT
  8. customEvaporation of the solvent, distribution between Et2O
  9. dry with materialan aqueous solution of NaOH, drying of the combined organic phases over Na2SO4 and chromatography on silica gel with heptane/EtOAc (gradient from 6:1 to 2:1)

Sources & evidence

ORD record
ord-47020953a69a4f0f9e1f02403498ad36
Source dataset
uspto-grants-2007_08
Patent number
US07253282B2

Reaction notes

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