Diisopropylethylamine → 2-{4-[(1-Ethoxycarbonyl-ethoxy)-methoxy-phosphoryl]-but-2-enyl}-6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic acid 2-trimethylsilanyl-ethyl Ester

HRID 33624

Reaction equation

HRID 33624 reaction equation
[CH3:1][Si:2]([CH3:44])([CH3:43])[CH2:3][CH2:4][O:5][C:6](=[O:42])[CH:7]([CH2:33][CH:34]=[CH:35][CH2:36][P:37]([OH:41])([O:39][CH3:40])=[O:38])[CH2:8][C:9]([CH3:32])=[CH:10][CH2:11][C:12]1[C:13]([O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])=[C:14]2[C:18](=[C:19]([CH3:23])[C:20]=1[O:21][CH3:22])[CH2:17][O:16][C:15]2=[O:24].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:78]([O:83][CH2:84][CH3:85])(=[O:82])[C@H:79]([CH3:81])O.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:44][Si:2]([CH3:43])([CH3:1])[CH2:3][CH2:4][O:5][C:6](=[O:42])[CH:7]([CH2:33][CH:34]=[CH:35][CH2:36][P:37]([O:41][CH:79]([C:78]([O:83][CH2:84][CH3:85])=[O:82])[CH3:81])([O:39][CH3:40])=[O:38])[CH2:8][C:9]([CH3:32])=[CH:10][CH2:11][C:12]1[C:13]([O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])=[C:14]2[C:18](=[C:19]([CH3:23])[C:20]=1[O:21][CH3:22])[CH2:17][O:16][C:15]2=[O:24]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 92831(L)-ethyl lactateHCID 2724699PyBOPHCID 765461902-[4-(Hydroxy-methoxy-phosphoryl)-but-2-enyl]-6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic acid 2-trimethylsilanyl-ethyl ester

Product 1

HCID 765410252-{4-[(1-Ethoxycarbonyl-ethoxy)-methoxy-phosphoryl]-but-2-enyl}-6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic acid 2-trimethylsilanyl-ethyl EsterYield 74.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-[4-(hydroxy-methoxy-phosphoryl)-but-2-enyl]-6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic acid 2-trimethylsilanyl-ethyl ester (67 mg, 0.10 mmol) and PyBOP (234 mg, 0.450 mmol) in DMF (1.5 mL) was stirred with ethyl (S)-(−)-lactate (53 mg, 0.45 mmol) and DIEA (174 μL, 1.00 mmol) at ambient temperature for 1 hour, when complete consumption of the starting materials was observed. The reaction was worked up by addition of saturated aqueous sodium chloride and ethyl acetate. The organic layer was separated and washed with 5% aqueous solution of lithium chloride. The organic layer was dried in vacuo and the residue was purified by silica gel chromatography using MeOH—CH2Cl2 (0-20%) to provide 57 mg (74%) of the desired product as a clear oil. 1H NMR (300 MHz, CDCl3) δ 0.02 (s, 9H), 0.05 (s, 9H), 0.88-0.94 (m, 2H), 1.20-1.30 (m, 2H), 1.29 (t, 3H, J=7 Hz), 1.45 (d, 3H, J=7 Hz), 1.78 (s, 3H), 2.01-2.31 (m, 4H), 2.17 (s, 3H), 2.50-2.58 (m, 1H), 2.65 (d, 1H, J=22 Hz), 2.67 (d, 1H, J=22 Hz), 3.39 (d, 2H, J=7 Hz), 3.69 and 3.77 (d, 3H, J=11 Hz), 3.76 (s, 3H), 4.07 (appt t, 2H, J=7 Hz), 4.20 (dq, 2H, J=3, 7 Hz), 4.29 (appt t, 2H, J=9 Hz), 4.85-4.99 (m, 1H), 5.12 (s, 2H), 5.19 (br t, 1H, J=6 Hz), 5.33-5.61 (m, 2H) ppm; 31P (121.4 MHz, CDCl3) δ 28.9, 29.9 ppm; MS (m/z) 791.4 [M+Na]+.

Workup

  1. customwhen complete consumption of the starting materials
  2. additionThe reaction was worked up by addition of saturated aqueous sodium chloride and ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with 5% aqueous solution of lithium chloride
  5. customThe organic layer was dried in vacuo
  6. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f99ad5352616428ebaaa2838ae0225ea
Source dataset
uspto-grants-2008_09
Patent number
US07429565B2

Linked notes

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