Ammonium Acetate → HCID 57610997, compound

HRID 80394Notes

Reaction equation

HRID 80394 reaction equation
C([O-])(=O)C.[NH4+:5].[CH3:6][O:7][C:8](=[O:35])[CH2:9][CH:10]([NH:20][C:21]([C@@H:23]1[CH2:27][CH2:26][CH2:25][N:24]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=O)[C:11]([C:13]1[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=1)=O>C1(C)C(C)=CC=CC=1.C(OCC)(=O)C>[Br:19][C:16]1[CH:17]=[CH:18][C:13]([C:11]2[N:5]=[C:21]([C@@H:23]3[CH2:27][CH2:26][CH2:25][N:24]3[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[NH:20][C:10]=2[CH2:9][C:8]([O:7][CH3:6])=[O:35])=[CH:14][CH:15]=1

Participants

5

Reactant 2

HCID 517165Ammonium AcetateHCID 57610926(2S)-tert-butyl 2-(4-(methoxy)-1-(4-bromophenyl)-1,4-dioxobutan-2-ylcarbamoyl)pyrrolidine-1-carboxylate

Product 1

HCID 57610997HCID 57610997, compoundYield 46.4%

Reagents, catalysts & solvents 2

HCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

Ammonium acetate (9.4 g, 157 mmol) was added to a solution of Example J7, (2S)-tert-butyl 2-(4-(methoxy)-1-(4-bromophenyl)-1,4-dioxobutan-2-ylcarbamoyl)pyrrolidine-1-carboxylate (7.6 g, 15.7 mmol) in xylene (80 mL) and stirred for 4 hours at 140° C. in a screw capped 150 mL pressure vessel. After being cooled, the reaction mixture was diluted with ethyl acetate and washed with sat NaHCO3 and brine before being concentrated by rotory evaporation under high vacuum. The crude product was taken up in CH2Cl2 and charged to a 40 (M) Biotage silica gel cartridge. Gradient elution 15-100% B over 2 L (A=CH2Cl2; B=ethyl acetate) gave Example J8, (S)-tert-butyl 2-(4-(4-bromophenyl)-5-(2-methoxy-2-oxoethyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate 3.38 g (46%). 1H NMR (500 MHz, DMSO-d6) δ 7.54 (s, 4H), 4.83-4.73 (m, 1H), 3.81 (br. s, 1H), 3.62 (s, 3H), 3.53-3.51 (m, 1H), 3.38-3.31 (m, 2H), 2.25-2.15 (m, 1H), 1.99-1.83 (m, 3H), 1.41/1.16 (s, 9H). RT=1.6 minutes (Condition 1). LCMS: Anal. Calcd. for C21H26BrN3O4 464.11; found: 464.40 (M+H)+.

Workup

  1. customcapped 150 mL pressure vessel
  2. temperatureAfter being cooled
  3. washwashed
  4. concentrationbefore being concentrated by rotory evaporation under high vacuum
  5. additioncharged to a 40 (M) Biotage silica gel cartridge
  6. washGradient elution 15-100% B over 2 L (A=CH2Cl2

Sources & evidence

ORD record
ord-5067955259464305958efb4ce825b5d4
Source dataset
uspto-grants-2014_09
Patent number
US08846023B2

Reaction notes

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