Toluene → 3-(3,5-Bis(trifluoromethyl)phenyl)-1-(4-tert-butylcyclohexyl)-1-{4-[1-hydroxy-2-(2H-tetrazol-5-yl)ethyl]benzyl}urea

HRID 480382Notes

Reaction equation

HRID 480382 reaction equation
CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.[F:29][C:30]([F:71])([F:70])[C:31]1[CH:32]=[C:33]([NH:41][C:42](=[O:69])[N:43]([CH:59]2[CH2:64][CH2:63][CH:62]([C:65]([CH3:68])([CH3:67])[CH3:66])[CH2:61][CH2:60]2)[CH2:44][C:45]2[CH:50]=[CH:49][C:48]([C:51](=[O:58])[CH2:52][C:53]3[N:54]=[N:55][NH:56][N:57]=3)=[CH:47][CH:46]=2)[CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1>C1COCC1>[F:71][C:30]([F:29])([F:70])[C:31]1[CH:32]=[C:33]([NH:41][C:42](=[O:69])[N:43]([CH:59]2[CH2:60][CH2:61][CH:62]([C:65]([CH3:66])([CH3:67])[CH3:68])[CH2:63][CH2:64]2)[CH2:44][C:45]2[CH:46]=[CH:47][C:48]([CH:51]([OH:58])[CH2:52][C:53]3[N:54]=[N:55][NH:56][N:57]=3)=[CH:49][CH:50]=2)[CH:34]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:36]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 187688993-(3,5-bis(trifluoromethyl)phenyl)-1-(4-tert-butylcyclohexyl)-1-[4-(2-2H-tetrazol-5-yl-acetyl)-benzyl]urea

Product 1

HCID 187689003-(3,5-Bis(trifluoromethyl)phenyl)-1-(4-tert-butylcyclohexyl)-1-{4-[1-hydroxy-2-(2H-tetrazol-5-yl)ethyl]benzyl}urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of (R)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c]-[1,3,2]oxazaborole in toluene (17 μl, 0.17 mmol, 1 M) in THF (1 ml) was added boran-THF complex (328 μl, 0.32 mmol, 1 M in THF). Then a solution of 3-(3,5-bis(trifluoromethyl)phenyl)-1-(4-tert-butylcyclohexyl)-1-[4-(2-2H-tetrazol-5-yl-acetyl)-benzyl]urea (100 mg, 0.17 mmol) in THF (1.0 ml) was added dropwise over a period of 30 min. The reaction mixture was stirred at room temperature overnight and then quenched with 1 N aqueous HCl (100 μl). Solvent was removed by rotary evaporation. The residue was dissolved in THF (500 μl) and injected into a preparative HPLC on a Gilson 2.11 with auto sampler (Xterra MS C18 5 μm 19 mm×100 mm, gradient: 10% acetonitrile in water→100% acetonitrile).

Workup

  1. customquenched with 1 N aqueous HCl (100 μl)
  2. customSolvent was removed by rotary evaporation
  3. dissolutionThe residue was dissolved in THF (500 μl)

Sources & evidence

ORD record
ord-779286a13a144f8389db7904c90ecc9f
Source dataset
uspto-grants-2003_11
Patent number
US06649641B2

Reaction notes

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