Ammonium fluoride → HCID 11179110, compound

HRID 1866493Notes

Reaction equation

HRID 1866493 reaction equation
[Si]([O:8][C@H:9]([C:34]1[CH:39]=[CH:38][C:37]([OH:40])=[C:36]([CH2:41][OH:42])[CH:35]=1)[CH2:10][NH:11][C:12]([CH3:33])([CH3:32])[CH2:13][C:14]1[CH:15]=[C:16]([CH:29]=[CH:30][CH:31]=1)[C:17]([NH:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=1)=[O:18])(C(C)(C)C)(C)C.[F-].[NH4+]>CO.O>[F:28][C:24]1[CH:23]=[C:22]([CH2:21][CH2:20][NH:19][C:17](=[O:18])[C:16]2[CH:29]=[CH:30][CH:31]=[C:14]([CH2:13][C:12]([NH:11][CH2:10][C@H:9]([OH:8])[C:34]3[CH:39]=[CH:38][C:37]([OH:40])=[C:36]([CH2:41][OH:42])[CH:35]=3)([CH3:33])[CH3:32])[CH:15]=2)[CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 2

HCID 25516Ammonium fluorideHCID 57978297HCID 57978297, compound

Product 1

HCID 11179110HCID 11179110, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

3-[2-({(2R)-2-{[tert-Butyl(dimethyl)silyl]oxy}-2-[4-hydroxy-3-(hydroxylmethyl)phenyl]ethyl}amino)-2-methylpropyl]-N-[2-(3-fluorophenyl)ethyl]benzamide (preparation 157), (343 mg, 0.58 mmol) and ammonium fluoride (213 mg, 5.76 mmol) in methanol (12 mL) and water (2 mL) were stirred at room temperature for 42 hours. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia, 100:0:0 to 90:10:1. The appropriate fractions were concentrated in vacuo and the residue was azeotroped (×2) in ethanol to give a white solid. This solid was then re-crystallised with ethanol/water and dried under vacuum to afford the title compound as very pale yellow crystals in 52% yield, 144 mg. 1H NMR (400 MHz, CD3OD) δ: 7.63 (2H, m) 7.38-7.23 (4H, m), 7.13 (1H, m), 7.05 (1H, m), 7.00 (1H, m), 6.91 (1H, m), 6.85 (1H, d), 4.65 (3H, m), 3.59 (2H, m), 2.96-2.84 (2H, m), 2.78-2.68 (2H, m), 1.10 (3H, s), 1.04 (3H, s) ppm. LRMS ESI m/z 481 [M+H]+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by column chromatography on silica gel
  3. washeluting with dichloromethane
  4. concentrationThe appropriate fractions were concentrated in vacuo
  5. customthe residue was azeotroped (×2) in ethanol
  6. customto give a white solid
  7. customThis solid was then re-crystallised with ethanol/water
  8. customdried under vacuum

Sources & evidence

ORD record
ord-05aa71ca97494566ad4c0496cc397011
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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