(L)-ethyl lactate → 2-{[4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyloxymethyl]-phenoxy-phosphinoyloxy}-propionic Acid Ethyl Ester

HRID 540686Notes

Reaction equation

HRID 540686 reaction equation
[C:1]1([O:7][P:8]([CH2:11][O:12][CH2:13][C:14]([CH3:31])=[CH:15][CH2:16][C:17]2[C:18]([OH:30])=[C:19]3[C:23](=[C:24]([CH3:28])[C:25]=2[O:26][CH3:27])[CH2:22][O:21][C:20]3=[O:29])(=[O:10])[OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:32]([O:37][CH2:38][CH3:39])(=[O:36])[C@H:33]([CH3:35])O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>N1C=CC=CC=1>[CH2:38]([O:37][C:32](=[O:36])[CH:33]([O:10][P:8]([CH2:11][O:12][CH2:13][C:14]([CH3:31])=[CH:15][CH2:16][C:17]1[C:18]([OH:30])=[C:19]2[C:23](=[C:24]([CH3:28])[C:25]=1[O:26][CH3:27])[CH2:22][O:21][C:20]2=[O:29])([O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:9])[CH3:35])[CH3:39]

Participants

5

Reactant 3

HCID 92831(L)-ethyl lactateHCID 2724699PyBOP2×HCID 76541028[4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyloxymethyl]-phosphonic acid monophenyl ester

Product 1

HCID 725636462-{[4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyloxymethyl]-phenoxy-phosphinoyloxy}-propionic Acid Ethyl EsterYield 34.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of [4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyloxymethyl]-phosphonic acid monophenyl ester (18.5 mg, 0.040 mmol) and ethyl (S)-(−)-lactate (47 μL, 0.400 mmol) in pyridine (0.5 mL) was added PyBOP (32 mg, 0.060 mmol). The solution was stirred at room temperature for 1 hour, when an additional portion of PyBOP (21 mg, 0.040 mmol) was added. The solution was stirred for another hour and concentrated. The residue was purified by HPLC to provide 7.5 mg of the desired product as a clear oil. 1H NMR (300 MHz, CD3OD) δ 1.22 and 1.25 (t, 3H, J=7 Hz), 1.42 and 1.50 (d, 3H, J=7 Hz), 1.82 and 1.83 (s, 3H), 2.16 (s, 3H), 3.47 (d, 2H, J=7 Hz), 3.78 (s, 3H), 3.89 (d, 1H, J=8 Hz), 3.93-4.02 (m, 3H), 4.10-4.22 (m, 2H), 4.94-5.08 (m, 1H), 5.25 (s, 2H), 5.50-5.60 (m, 1H), 7.15-7.27 (m, 3H), 7.33-7.41 (m, 2H) ppm; 31P (121.4 MHz, CD3OD) δ 18.9, 20.3 ppm (diastereomers at phosphorus); MS (m/z) 549.2 [M+H]+, 571.3 [M+Na]+.

Workup

  1. stirringThe solution was stirred for another hour
  2. concentrationconcentrated
  3. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-ee6d024cf1f14c4c9d18df9ecd78b4f0
Source dataset
uspto-grants-2014_10
Patent number
US08871785B2

Reaction notes

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