Sodium Carbonate → HCID 67414081, compound

HRID 2273052Notes

Reaction equation

HRID 2273052 reaction equation
FC(F)(F)S(O[C:7]1[CH2:12][CH2:11][CH:10]([NH:13][C:14]([C@@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:15])[CH2:9][CH:8]=1)(=O)=O.CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[NH:48][C:47]([C@@H:49]4[CH2:53][CH2:52][CH2:51][N:50]4[C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])=[N:46][CH:45]=3)=[CH:40][CH:39]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:57]([O:56][C:54]([N:50]1[CH2:51][CH2:52][CH2:53][C@H:49]1[C:47]1[NH:48][C:44]([C:41]2[CH:42]=[CH:43][C:38]([C:7]3[CH2:12][CH2:11][CH:10]([NH:13][C:14]([C@@H:16]4[CH2:20][CH2:19][CH2:18][N:17]4[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:15])[CH2:9][CH:8]=3)=[CH:39][CH:40]=2)=[CH:45][N:46]=1)=[O:55])([CH3:60])([CH3:58])[CH3:59]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 56605289(s)-tert-Butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1h-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 89056391HCID 89056391, compound

Product 1

HCID 67414081HCID 67414081, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (25)-tert-butyl 2-(4-(trifluoromethylsulfonyloxy)cyclohex-3-enyl carbamoyl)pyrrolidine-1-carboxylate (2) (1.65 g, 3.73 mmol) and (5)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (3) (1.95 g, 4.44 mmol) in THF (19 mL), Pd(PPh3)2Cl2 (130 mg, 0.185 mmol) and aqueous Na2CO3 (2M, 7.5 mL, 15 mmol) were added under N2 protection at rt. The reaction mixture was heated at 80° C. overnight, and cooled to rt. The mixture was then filtered through a CELITE™ pad and washed with ethyl acetate. The combined organic phases were concentrated to provide the crude product, which was purified by silica gel column chromatography (n-hexane/ethyl acetate, 1:2) to afford (2S)-tert-butyl 2-(4-(4-(2-((5)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)cyclohex-3-enylcarbamoyl)pyrrolidine-1-carboxylate (4) (2.1 g, 93% yield).

Workup

  1. temperaturecooled to rt
  2. filtrationThe mixture was then filtered through a CELITE™ pad
  3. washwashed with ethyl acetate
  4. concentrationThe combined organic phases were concentrated
  5. customto provide the crude product, which
  6. customwas purified by silica gel column chromatography (n-hexane/ethyl acetate, 1:2)

Sources & evidence

ORD record
ord-c4da8e4ac16a42f3978c12550e1443b5
Source dataset
uspto-grants-2015_09
Patent number
US09120779B2

Reaction notes

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