HCID 91406395, compound → HCID 86603402, compound

HRID 1994460Notes

Reaction equation

HRID 1994460 reaction equation
C[O:2][C:3](=O)[CH:4]([C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=1)[NH:5][CH2:6][C:7]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=1[C:17]1[CH:22]=[C:21]([CH:23]([CH3:25])[CH3:24])[CH:20]=[CH:19][C:18]=1[O:26][CH3:27]>CCOCC.[H-].[H-].[H-].[H-].[Li+].[Al+3]>[F:35][C:34]([F:36])([F:37])[C:32]1[CH:33]=[C:28]([CH:4]([NH:5][CH2:6][C:7]2[CH:12]=[C:11]([C:13]([F:14])([F:15])[F:16])[CH:10]=[CH:9][C:8]=2[C:17]2[CH:22]=[C:21]([CH:23]([CH3:24])[CH3:25])[CH:20]=[CH:19][C:18]=2[O:26][CH3:27])[CH2:3][OH:2])[CH:29]=[C:30]([C:38]([F:39])([F:40])[F:41])[CH:31]=1

Participants

4

Reactant 1

HCID 91406395HCID 91406395, compound

Product 1

HCID 86603402HCID 86603402, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21226445Aluminium lithium hydrideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of methyl[3,5-bis(trifluoromethyl)phenyl]({[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)acetate (13.2 mg, 0.0217 mmol) was dissolved in Et2O (1.5 mL) and cooled to 0° C. LAH (108.5 μL of a 1 M solution in LAH, 0.1085 mmol) was added dropwise by syringe. The reaction was warmed to room temperature and stirred at room temperature for 1 hour. The reaction was then quenched by addition of H2O (100 μL) followed by 1 N NaOH (100 μL), followed by H2O (300 mL). The gelatinous precipitate was washed several times with CH2Cl2. The organic washes were filtered through a plug of silica gel with 2% MeOH/CH2Cl2 and the filtrate was concentrated. Purification of the residue by PTLC with 25% EtOAc/hexanes afforded 2-[3,5-bis(trifluoromethyl)phenyl]-2-({[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)ethanol. Rf=0.27 (25% EtOAc/hexanes). LCMS=580.4 (M+1)+. 1H NMR (CD2Cl2, 500 MHz) δ 7.79 (s, 1H), 7.75 (s, 2H), 7.63-7.68 (m, 1H), 7.55 (d, J=7.8 Hz, 1H), 7.31 (d, J=7.8 Hz, 1H), 7.23 (m, 1H), 6.94 (m, 1H), 6.89 (m, 1H), 3.43-3.76 (m, 9H), 2.86 (m, 1H), 1.90 (bs, 1H), 1.20 (d, J=6.8 Hz, 6H).

Workup

  1. temperatureThe reaction was warmed to room temperature
  2. customThe reaction was then quenched by addition of H2O (100 μL)
  3. washThe gelatinous precipitate was washed several times with CH2Cl2
  4. filtrationThe organic washes were filtered through a plug of silica gel with 2% MeOH/CH2Cl2
  5. concentrationthe filtrate was concentrated
  6. customPurification of the residue by PTLC with 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-9fc36b2f94ff4793a2ca0c88cf10d1dd
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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