Ethyl Acetate → Benzyl 3-(2-propionyloxy-5-(ethoxy(diethylphosphonomethyl)phosphinoyl)phenyl)-3-methylbutanoate

HRID 39278Notes

Reaction equation

HRID 39278 reaction equation
[C:1](Cl)(=[O:4])[CH2:2][CH3:3].[OH:6][C:7]1[CH:12]=[CH:11][C:10]([P:13]([O:24][CH2:25][CH3:26])([CH2:15][P:16]([O:21][CH2:22][CH3:23])([O:18][CH2:19][CH3:20])=[O:17])=[O:14])=[CH:9][C:8]=1[C:27]([CH3:40])([CH3:39])[CH2:28][C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30].C(OCC)(=O)C>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[C:1]([O:6][C:7]1[CH:12]=[CH:11][C:10]([P:13]([O:24][CH2:25][CH3:26])([CH2:15][P:16]([O:21][CH2:22][CH3:23])([O:18][CH2:19][CH3:20])=[O:17])=[O:14])=[CH:9][C:8]=1[C:27]([CH3:40])([CH3:39])[CH2:28][C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30])(=[O:4])[CH2:2][CH3:3]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 62324Propionyl chlorideHCID 25139361Benzyl 3-(2-hydroxy-5-(Ethoxy(diethylphosphonomethyl)phosphinoyl)phenyl)-3-methylbutanoate

Product 1

HCID 86655577Benzyl 3-(2-propionyloxy-5-(ethoxy(diethylphosphonomethyl)phosphinoyl)phenyl)-3-methylbutanoateYield 66.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

Proprionyl chloride (190 μL, 2.17 mmol) was added drop-wise to a stirring solution of crude phenol 122 (880 mg, 1.67 mmol) and DMAP (2 mg, 0.016 mmol) in pyridine (5 mL). The reaction was continued for 3 hr at room temperature followed by the addition of ethyl acetate (100 mL). The organic layer was washed with cold aqueous HCl (0.5 N), H2O and saturated aqueous NaCl then dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography (0 to 20% methanol in ethyl acetate) using a Biotage Horizons™ system, resulting in 123 as a pale yellow liquid (644 mg, 66%): 1H NMR (400 MHz, CDCl3) δ 1.25 (t, J=7.0, 3H), 1.26 (t, J=7.5, 3H), 1.30 (t, J=7.0, 3H), 1.46 (s, 3H), 1.48 (s, 3H), 2.50-2.63 (m, 4H), 2.82 (AB q, J=14.4, 2H), 3.93-4.16 (m, 6H), 4.93 (s, 2H), 7.12-7.18 (m, 3H), 7.26-7.32 (m, 3H), 7.70 (ddd, J=1.8, 8.4, 11.6, 1H), 7.86 (dd, J=1.8, 13.4, 1H): 31P (162 MHz, CDCl3) δ 20.21 (d, J=9.7, 1 P), 34.03 (d, J=9.7, 1 P).

Workup

  1. washThe organic layer was washed with cold aqueous HCl (0.5 N), H2O and saturated aqueous NaCl
  2. dry with materialthen dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by silica gel chromatography (0 to 20% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-59f6858b49044c839b8d0114e1657121
Source dataset
uspto-grants-2013_09
Patent number
US08524691B2

Reaction notes

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