Benzyl Bromide → Benzyl 3-(2-hydroxy-5-(Ethoxy(diethylphosphonomethyl)phosphinoyl)phenyl)-3-methylbutanoate

HRID 39277Notes

Reaction equation

HRID 39277 reaction equation
[OH-].[K+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([P:10]([O:21][CH2:22][CH3:23])([CH2:12][P:13]([O:18][CH2:19][CH3:20])([O:15][CH2:16][CH3:17])=[O:14])=[O:11])=[CH:6][C:5]=1[C:24]([CH3:30])([CH3:29])[CH2:25][C:26]([OH:28])=[O:27].[CH2:31](Br)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(#N)C>[OH:3][C:4]1[CH:9]=[CH:8][C:7]([P:10]([O:21][CH2:22][CH3:23])([CH2:12][P:13]([O:18][CH2:19][CH3:20])([O:15][CH2:16][CH3:17])=[O:14])=[O:11])=[CH:6][C:5]=1[C:24]([CH3:30])([CH3:29])[CH2:25][C:26]([O:28][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:27]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 14797Potassium HydroxideHCID 251407843-(2-Hydroxy-5-(Ethoxy(diethylphosphonomethyl)phosphinoyl)phenyl)-3-methylbutanoic acid

Product 1

HCID 25139361Benzyl 3-(2-hydroxy-5-(Ethoxy(diethylphosphonomethyl)phosphinoyl)phenyl)-3-methylbutanoateYield 48%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

An aqueous KOH solution (0.14 g, 2.5 mmol) was added to a stirring solution of 121 (1.1 g, 2.5 mmol) in acetonitrile (5 mL). After 10 min the solvent was evaporated under reduced pressure and the residue was dried under vacuum for 1 hr. The pale yellow solid was resuspended in DMF (10 mL) followed by the addition of benzylbromide (330 μL, 2.8 eq). The resulting solution was stirred at room temperature for 2 hr. The mixture was diluted with EtOAC (80 mL) and washed with H2O and saturated aqueous NaCl, followed by drying over Na2SO4. The crude product was purified by silica gel chromatography (0-10% methanol in CH2Cl2) on a Biotage™ flash chromatography system, resulting in 122 as a pale yellow liquid (0.64 g, 48%): 1H NMR (400 MHz, CDCl3) δ 1.23 (t, J=7.1, 3H), 1.26 (t, J=7.1, 3H), 1.30 (t, J=7.1, 3H), 1.45 (s, 3H), 1.49 (s, 3H), 2.60 (dd, J=17.4, 20.9, 2H), 3.00 (AB q, J=14.0, 2H), 3.78-3.88 (m, 2H), 3.99-4.15 (m, 4H), 4.93 (s, 2H), 6.75-6.78 (m, 1H), 7.14 (dd, J=2.0, 7.5, 2H), 7.25-7.31 (m, 3H), 7.58 (ddd, J=1.4, 8.0, 11.9, 1H), 7.64 (d, J=13.4, 1H): 31P (162 MHz, CDCl3) δ 21.04 (d, J=4.6, 1 P), 36.00 (d, J=4.6, 1 P).

Workup

  1. customAfter 10 min the solvent was evaporated under reduced pressure
  2. customthe residue was dried under vacuum for 1 hr
  3. additionThe mixture was diluted with EtOAC (80 mL)
  4. washwashed with H2O and saturated aqueous NaCl
  5. dry with materialby drying over Na2SO4
  6. customThe crude product was purified by silica gel chromatography (0-10% methanol in CH2Cl2) on a Biotage™ flash chromatography system

Sources & evidence

ORD record
ord-0ebcb49c209f4e29bc3ee4a6d1286170
Source dataset
uspto-grants-2013_09
Patent number
US08524691B2

Reaction notes

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