Sodium Hydroxide → Ammonium Acetate

HRID 871106Notes

Reaction equation

HRID 871106 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13]3=[N:14][C:15]([C:18]4[C:19]5[CH:26]=[C:25]([C:27]6[CH2:28][N:29](C([O:35][C:36]([CH3:39])(C)C)=O)[CH2:30][CH2:31][CH:32]=6)[N:24](S(C6C=CC(C)=CC=6)(=O)=O)[C:20]=5[N:21]=[CH:22][CH:23]=4)=[CH:16][CH:17]=[C:12]3[CH:11]=[CH:10]2)[CH:5]=[N:6][CH:7]=1.[OH-:50].[Na+]>O1CCCC1.CO>[C:36]([O-:35])(=[O:50])[CH3:39].[NH4+:6].[F:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13]3=[N:14][C:15]([C:18]4[C:19]5[CH:26]=[C:25]([C:27]6[CH2:28][NH:29][CH2:30][CH2:31][CH:32]=6)[NH:24][C:20]=5[N:21]=[CH:22][CH:23]=4)=[CH:16][CH:17]=[C:12]3[CH:11]=[CH:10]2)[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 90408202HCID 90408202, compound

Product 2

HCID 517165Ammonium AcetateHCID 90408602HCID 90408602, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example 56B (470 mg, ˜0.55 mmol) in 5 mL tetrahydrofuran and 3.5 mL methanol was added aqueous sodium hydroxide (1 M, 2.08 mL, 2.08 mmol). The reaction mixture was stirred at room temperature for 16 hours and concentrated. To the residue was added 2 mL dichloromethane and 1 mL trifluoroacetic acid. The mixture was stirred at room temperature for 40 minutes. The reaction was concentrated then purified by reverse-phase HPLC performed on a Phenomenex Luna C8 AXIA column (30×75 mm, 100 Å) using a gradient of 10% to 95% acetonitrile:10 mM ammonium acetate in water to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.24-2.36 (m, 2 H) 2.97 (t, J=5.65 Hz, 2 H) 3.66-3.71 (m, 2 H) 5.70 (s, 2 H) 6.60-6.69 (m, 2 H) 7.03 (s, 1 H) 7.54-7.69 (m, 2 H) 7.83 (d, J=3.36 Hz, 1 H) 7.88 (d, J=8.24 Hz, 1 H) 8.17 (d, J=8.24 Hz, 1 H) 8.28 (d, J=5.19 Hz, 1 H) 8.41-8.56 (m, 2 H) 11.86 (s, 1 H). MS (ESI) m/e 425 (M+H)+.

Workup

  1. concentrationconcentrated
  2. additionTo the residue was added 2 mL dichloromethane and 1 mL trifluoroacetic acid
  3. stirringThe mixture was stirred at room temperature for 40 minutes
  4. concentrationThe reaction was concentrated
  5. customthen purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-bc03225c426d49ca8640f8b48f591e66
Source dataset
uspto-grants-2015_03
Patent number
US08969375B2

Reaction notes

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