Acetic Acid → HCID 89662814, compound

HRID 1479080Notes

Reaction equation

HRID 1479080 reaction equation
Cl.[Cl:2][C:3]1[C:11]([CH3:12])=[N:10][C:9]2[N:5]([N:6]=[C:7]3[C:15]([CH3:17])([CH3:16])[N:14]([C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[O:19])[CH2:13][C:8]3=2)[C:4]=1[CH3:33].C=O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O.[OH-].[Na+]>ClCCCl>[Cl:2][C:3]1[C:11]([CH3:12])=[N:10][C:9]2[N:5]([N:6]=[C:7]3[C:15]([CH3:16])([CH3:17])[N:14]([C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH:27]4[CH2:28][CH2:29][N:30]([CH3:36])[CH2:31][CH2:32]4)=[O:19])[CH2:13][C:8]3=2)[C:4]=1[CH3:33]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 122429360HCID 122429360, compound

Product 1

HCID 89662814HCID 89662814, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of Example 100 (100 mg; 0.22 mmol; 1 eq.), paraformaldehyde (60 mg; 0.66 mmol; 3 eq.), sodium triacetoxyborohydride (93 mg; 0.44 mmol; 2 eq.) and AcOH (13 μL; 0.22 mmol; 1 eq.) in DCE (5 mL) was stirred at 65° C. for 16 hours. 1M NaOH was added and the two phases separated. The aqueous layer was extracted with DCM (2×). The combined organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (5% to 20% MeOH in DCM) afforded the title compound (82 mg, 80%) as a colourless oil. 1H NMR (DMSO-d6) δ 7.44-7.32 (m, 1H), 7.24 (dd, J=7.4, 1.7 Hz, 1H), 7.16 (d, J=8.2 Hz, 1H), 7.06-6.96 (m, 1H), 4.58-4.42 (m, 2H), 4.42-4.25 (m, 1H), 2.83 (s, 3H), 2.54 (s, 3H), 2.48-2.34 (m, 2H), 2.15 (br s, 2H), 2.04 (s, 3H), 1.94-1.75 (m, 8H), 1.56 (br s, 2H). HPLC (max plot) 98.6%, Rt 3.15 min. UPLC/MS: (MS+) 468.5 ([M+H]+).

Workup

  1. customthe two phases separated
  2. extractionThe aqueous layer was extracted with DCM (2×)
  3. dry with materialThe combined organic phase was dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by column chromatography (5% to 20% MeOH in DCM)

Sources & evidence

ORD record
ord-7984a92de13247db919d36bc6693624b
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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