Acetic Acid → HCID 44581496, compound

HRID 971149Notes

Reaction equation

HRID 971149 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]3[C:14](=[O:29])[N:15]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5([NH:27][CH3:28])[CH2:26][CH2:25]5)=[CH:20][CH:19]=4)[CH2:16][CH2:17][C:12]=3[C:11]([C:30]([F:33])([F:32])[F:31])=[N:10]2)=[CH:5][CH:4]=1.C=O.[CH3:36]C(O)=O.[BH3-]C#N.[Na+].[OH-].[Na+]>CC#N.CC(C)=O>[CH3:28][N:27]([CH3:36])[C:24]1([C:21]2[CH:22]=[CH:23][C:18]([N:15]3[CH2:16][CH2:17][C:12]4[C:11]([C:30]([F:32])([F:33])[F:31])=[N:10][N:9]([C:6]5[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=5)[C:13]=4[C:14]3=[O:29])=[CH:19][CH:20]=2)[CH2:26][CH2:25]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 44581495HCID 44581495, compound

Product 1

HCID 44581496HCID 44581496, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 180AcetoneCatalystHCID 6342AcetonitrileSolvent

Procedure

The product from Example 130 (30 mg, 0.066 mmol) was stirred in CH3CN (0.2 mL) at rt under N2. Aqueous formaldehyde (0.07 mL, 7 mmol, 10 eq) was added followed by the addition of HOAc (0.012 mL, 0.21 mmol, 3.2 eq). The mixture was stirred for 15 min, and then NaBH3CN (12 mg, 0.198 mmol) was added. The mixture was stirred at rt for 2 h. Several drops of acetone were added followed by 1N NaOH. The mixture was extracted with CH2Cl2, washed with H2O and brine, dried over MgSO4, and concentrated to dryness. The residue was purified by FCC (silica gel, EtOAc, than EtOAc:MeOH=10:1) to yield the title compound (15.7 mg, 51%). 1H NMR (CDCl3) δ 7.46 (d, J=8.8 Hz, 2H), 7.29 (m, 4H), 6.92 (d, J=9.2 Hz, 2H), 4.15 (t, J=6.6 Hz, 2H), 3.81 (s, 3H), 3.16 (t, J=6.6 Hz, 2H), 2.28 (s, 6H), 1.02 (m, 2H), 0.81 (m, 2H) ppm. LC/MS (ESI+) 471.4.

Workup

  1. stirringThe mixture was stirred at rt for 2 h
  2. extractionThe mixture was extracted with CH2Cl2
  3. washwashed with H2O and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by FCC (silica gel, EtOAc, than EtOAc:MeOH=10:1)

Sources & evidence

ORD record
ord-47f4d85d5779489eb00f1440241106ab
Source dataset
uspto-grants-2007_12
Patent number
US07312214B2

Reaction notes

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