tert-Butanol → HCID 66740647, compound

HRID 83928Notes

Reaction equation

HRID 83928 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][CH2:12][C:13]1[N:14]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:20])[CH3:19])=[CH:16][N:17]=1)C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:45])C=CC=CC=1.CC[N:57]([CH:61](C)C)C(C)C.[C:64]([OH:68])([CH3:67])([CH3:66])[CH3:65]>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:57][C:61](=[O:45])[O:68][C:64]([CH3:67])([CH3:66])[CH3:65])[CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][CH2:12][C:13]1[N:14]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:19])[CH3:20])=[CH:16][N:17]=1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 667403173-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-(4-fluorophenyl)-1H-imidazol-2-yl)ethyl)-5-fluorobenzoic acid

Product 1

HCID 66740647HCID 66740647, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To solution of 3-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)ethyl)-5-fluorobenzoic acid (540 mg) in a mixture of toluene (5 mL) and tert-butanol (1.5 mL) cooled to 0° C. was added diphenyl phosphoryl azide (DPPA) (1.1 eq, 302 mg) followed by DIPEA (1.3 eq, 226 μL). During addition of base, the white slurry became a clear solution, which was heated at 80° C. After 16 h, complete conversion was observed by LC-MS. The reaction was diluted with EtOAc, washed with satd NaHCO3, dried (Na2SO4), concentrated and purified by chromatography (silica, EtOAc/Hex, 10-60%) to yield tert-butyl 3-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)ethyl)-5-fluorophenylcarbamate (230 mg). MS (EI) m/z 616 (MH+).

Workup

  1. additionDuring addition of base
  2. temperaturewas heated at 80° C
  3. washwashed with satd NaHCO3
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by chromatography (silica, EtOAc/Hex, 10-60%)

Sources & evidence

ORD record
ord-959baa3de8fe47649c253106b00405e8
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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