Diisopropylethylamine → HCID 86603407, compound

HRID 1028502Notes

Reaction equation

HRID 1028502 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([CH:13]([OH:38])[CH2:14][NH:15][CH2:16][C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=2[C:27]2[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[CH:30]=[CH:29][C:28]=2[O:36][CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[O:41](C(OC(C)(C)C)=O)[C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=O.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:45]([O:44][C:42](=[O:41])[N:15]([CH2:14][CH:13]([C:5]1[CH:4]=[C:3]([C:2]([F:39])([F:40])[F:1])[CH:8]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:6]=1)[OH:38])[CH2:16][C:17]1[CH:22]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:20]=[CH:19][C:18]=1[C:27]1[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[CH:30]=[CH:29][C:28]=1[O:36][CH3:37])([CH3:48])([CH3:47])[CH3:46]

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 90495Di-tert-butyl dicarbonate2×HCID 86603405HCID 86603405, compound

Product 1

HCID 86603407HCID 86603407, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[3,5-bis(trifluoromethyl)phenyl]-2-({[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)ethanol (Example 6 Step B, 325.0 mg, 0.561 mmol) in CH2Cl2 (15 mL) was added BOC2O (122 mg, 0.561 mmol) and DIPEA (98 μL, 0.561 mmol). The reaction was stirred at room temperature. After 5 hours, additional BOC2O (50 mg, 0.229 mmol) and DIPEA (50 μL, 0.287 mmol) were added. The reaction was stirred at room temperature for 48 hours. The reaction was then concentrated to ˜2 mL, diluted with hexanes (8 mL) and purified by flash chromatography with 10 to 20% EtOAc/hexanes to afford tert-butyl{2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxyethyl}{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate. Rf=0.38 (25% EtOAc/hexanes). LCMS=580.3 (M+1−BOC)+. 1H NMR (CD2Cl2, 500 MHz) δ 7.78 (s, 1H), 7.54-7.67 (m, 4H), 7.23-7.33 (m, 2H), 6.90-6.95 (m, 2H), 3.15-4.82 (m, 9H), 2.87 (m, 1H), 1.19-1.43 (m, 15 H).

Workup

  1. stirringThe reaction was stirred at room temperature for 48 hours
  2. concentrationThe reaction was then concentrated to ˜2 mL
  3. additiondiluted with hexanes (8 mL)
  4. custompurified by flash chromatography with 10 to 20% EtOAc/hexanes

Sources & evidence

ORD record
ord-aedfdab0cc7a4928aa369470a85fe185
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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