Acetic Acid → HCID 178452510, compound

HRID 1751614Notes

Reaction equation

HRID 1751614 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Br:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:13][C:14]([C@@H:16]1[C@H:21]2[CH2:22][C@H:18]([CH2:19][CH2:20]2)[N:17]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=O.CC(O)=O.[OH-].[Na+]>C(OCC)(=O)C>[Br:12][C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]1[NH:1][C:14]([C@@H:16]3[C@H:21]4[CH2:22][C@H:18]([CH2:19][CH2:20]4)[N:17]3[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[N:13][C:3]=1[CH:4]=[CH:5]2

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 86708790(1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

Product 1

HCID 178452510HCID 178452510, compoundYield 93.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

(1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (2.01 g, 4.36 mmol) was suspended in AcOH (8.73 mL, 152.7 mmol) and placed in a preheated 50° C. oil bath. The suspension was let stir at 50° C. for 4 hours and at room temperature for 14 hours. Upon completion, the reaction mixture was diluted with ethyl acetate and aqueous NaOH (6M, 25.4 mL, 152.7 mmol) was added slowly with stirring. The layers were separated and the aqueous layer was back extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The resulting oil was purified by normal phase chromatography (30-55-100% ethyl acetate (5% MeOH) in hexanes) to give (1S,3S,4R)-tert-butyl 3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (1.8 g, 93%). LCMS-ESI+: calc'd for C22H24BrN3O2: 441.11 (M+); Found: 442.7 (M+H+).

Workup

  1. customplaced in a preheated 50° C.
  2. additionwas added slowly
  3. stirringwith stirring
  4. customThe layers were separated
  5. extractionthe aqueous layer was back extracted with ethyl acetate twice
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resulting oil was purified by normal phase chromatography (30-55-100% ethyl acetate (5% MeOH) in hexanes)

Sources & evidence

ORD record
ord-bdf5059cfacb4fd4bc156d2caed49e86
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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