Isobutanol → HCID 10145143, compound

HRID 895340Notes

Reaction equation

HRID 895340 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[CH2:6][O:7][CH2:8][CH:9]([N:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][O:24][CH2:25][C:26]([OH:28])=[O:27])[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH2:38](O)[CH:39]([CH3:41])[CH3:40].CCN=C=NCCCN(C)C>C1COCC1.CN(C1C=CN=CC=1)C>[CH2:38]([O:27][C:26](=[O:28])[CH2:25][O:24][CH2:23][CH2:22][N:19]1[CH2:18][CH2:17][N:16]([CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][O:7][CH2:6][C:5]2[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=[C:3]([C:2]([F:1])([F:36])[F:37])[CH:4]=2)[CH2:21][CH2:20]1)[CH:39]([CH3:41])[CH3:40]

Participants

6

Reactant 3

HCID 6560IsobutanolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 10230370HCID 10230370, compound2×

Product 1

HCID 10145143HCID 10145143, compoundYield 78.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In a round-bottomed flask fitted with a reflux condenser and a thermometer were introduced (2-{4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazin-1-yl}-ethoxy)-acetic acid (compound 235, 0.5 g, 0.84 mmoles) dissolved in THF (20 ml). To this solution cooled at 0° C. were successively added isobutanol (0.155 ml, 1.68 mmoles), DMAP (0.01 g, 0.084 mmoles) and EDCI (0.177 g, 0.93 mmoles). The reaction mixture was stirred for 2 hours at 0° C. and then allowed to reach room temperature and stirred overnight. The organic solution was washed with HCl 0.1N and water, dried over MgSO4 and concentrated. The resulting oil was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/NH3: 99.5/0.5/0.1 v/v/v) to yield (2-{4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazin-1-yl}-ethoxy)-acetic acid isobutyl ester (compound 287, 390 mg, 65%) which was converted into its dihydrochloride monohydrate salt by reaction with HCl in diethylether.

Workup

  1. customIn a round-bottomed flask fitted with a reflux condenser
  2. customto reach room temperature
  3. stirringstirred overnight
  4. washThe organic solution was washed with HCl 0.1N and water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe resulting oil was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/NH3: 99.5/0.5/0.1 v/v/v)

Sources & evidence

ORD record
ord-1f87ad1838f14302bbccb32578aa20d4
Source dataset
uspto-grants-2005_07
Patent number
US06916797B2

Reaction notes

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