A straightforward and general access to α-phthalimido-α′- substituted propan-2-ones

Article abstract of DOI:10.1016/j.tetlet.2012.07.045

The regioselective ring opening of the commercially available N-(2,3-epoxypropyl)phthalimide with different nucleophiles, to obtain the corresponding phthalimidopropan-2-ols (including a challenging fluorohydrin) followed by the Dess-Martin periodinane ox

Full text of DOI:10.1016/j.tetlet.2012.07.045

Supporting Information
For
A straightforward and general access to α-phthalimido-α’-substituted
propan-2-ones
Vittorio Pace*a,b and Wolfgang Holzerb
aOrganic and Pharmaceutical Chemistry Department, Faculty of Pharmacy, Complutense
University of Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.
bDepartment of Drug and Natural Product Synthesis, University of Vienna, Althanstrasse 14,
1090 Vienna, Austria.
*Corresponding Author: Email: vpace@farm.ucm.es; Fax: +43-1-4277-55623; Tel: +43-1-
4277-9556.
Materials and Instrumentation.
1H NMR, 13C NMR and 19F NMR were recorded on a Bruker AC-250 spectrometer at 250 MHz,
at 62.5 MHz and at 235 MHz respectively, from CDCl3 solutions at 25 °C. The center of the
(residual) solvent signal was used as an internal standard which was related to TMS with δ 7.26
ppm (1H) and δ 77.0 ppm (13C). Spin-spin coupling constants (J) are given in Hz. IR absorption
spectra were recorded as NaCl pellets on a Shimadzu FT-IR 8400S (E41107). Spectra analyses
were performed with the software Shimadzu IRsolution (Version 1.21, 2005). Elementary
microanalyses were carried out using a Leco® CHNS 932 equipment. Column chromatography
purifications were conducted on silica gel 60 (40-63 μm). Melting points are uncorrected.
Solutions were evaporated under reduced pressure with a rotary evaporator and the residue was
chromatographed on a silica gel column using ethyl acetate / hexanes mixture as the eluent
unless otherwise specified. TLC was carried out on aluminium sheets precoated with silica gel
60F254 (Macherey-Nagel, Merk); the spots were visualised under UV light (λ = 254 nm) and/or
KMnO4 (aq.) was used as revealing system. All chemicals were purchased from Sigma Aldrich,
Acros and Alfa Aesar and solvents were purified by distillation immediately before use
according standard procedures.

Preparation of aminoalcohols 3a-e via formal addition of HX acid. (General Procedure A)
To a solution of 2,3-epoxypropylphthalimide (2) (1.0 equiv.), in chloroform (10 mL) cooled at
0°C, a concentrated solution of hydrohalic acid (2.0 equiv.) was added dropwise. The mixture
was allowed to react during 0.5-6 h (Table 1) and, therefore it was washed with saturated
aqueous NaCl and extracted twice with dichloromethane. Organic phases were dried over
anhydrous sodium sulfate, filtered and after removal of the organic solvents in vacuo pure
compounds were obtained without needing of further purification.
2-(3-chloro-2-hydroxypropyl)-1H-isoindole-1,3(2H)-dione (3a).
By following the General Procedure A, starting from 1 (4.00 mmol, 820 mg) and HCl 37% (6
mL), compound 3a was obtained in quantitative yield (958 mg) as a white solid, mp 95°C (lit.1,
95°C)
IR (NaCl) 3313, 1772, 907, 730, 653 cm-1.
1H NMR (250 MHz, CDCl3) δ 3.01 (bs, 1H), 3.70 (dd, J = 5.2 Hz, J = 11.3 Hz, 2H), 4.04 (dd, J
= 14.1 Hz, J = 23.3 Hz, 2H), 4.21-4.30 (m, 1H), 3.98-4.11 (m, 1H), 7.78 (dd, J = 3.0 Hz, J = 5.1
Hz, 2H), 7.90 (dd, J = 3.0 Hz, J = 5.2 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 41.6, 47.3, 69.8, 123.6, 131.9, 134.4, 168.7.
Anal. Calcd. for C11H10ClNO3: C, 55.13; H, 4.21; N, 5.84. Found: C, 55.42; H, 4.38; N, 5.99.
2-(3-bromo-2-hydroxypropyl)-1H-isoindole-1,3(2H)-dione (3b).
By following the General Procedure A, starting from 2 (4.00 mmol, 820 mg) and HBr 48% (6
mL), compound 3b was obtained in 98% yield (1113 mg), mp 114-115°C.
IR (NaCl) 3309, 1769, 902, 730, 651 cm-1.
1H NMR (250 MHz, CDCl3) 2.84 (bs, 1H), 3.50 (dd, J = 5.2 Hz, J = 11.3 Hz, 2H), 3.90 (dd, J =
14.1 Hz, J = 23.3 Hz, 2H), 4.10-4.27 (m, 1H), 7.78 (dd, J = 3.0 Hz, J = 5.1 Hz), 7.88 (dd, J =
3.0 Hz, J = 5.2 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 36.6, 42.3, 69.7, 124.1, 132.2, 134.1, 168.9.
Anal. Calcd. for C11H10BrNO3: C, 46.50; H, 3.55; N, 4.93. Found: C, 46.71; H, 3.73; N, 5.08.

2-(2-hydroxy-3-iodopropyl)-1H-isoindole-1,3(2H)-dione (3c).
By following the General Procedure A, starting from 2 (4.00 mmol, 820 mg) and HI 57% (5
mL), compound 3c was obtained in quantitative yield (1324 mg) as a brown syrup.
IR (NaCl) 3334, 1773, 904, 725, 649 cm-1.
1H NMR (250 MHz, CDCl3) 2.85 (bs, 1H), 3.34 (dd, J = 4.6 Hz, J = 10.8 Hz, 2H), 3.86-3.97 (m,
3H), 7.74 (dd, J = 3.1 Hz, J = 5.1 Hz), 7.85 (dd, J = 3.1 Hz, J = 5.2 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 10.7, 42.2, 43.6, 69.4, 123.6, 131.9, 134.2, 168.6.
Anal. Calcd. for C11H10INO3: C, 39.90; H, 3.04; N, 4.23. Found: C, 40.09; H, 3.33; N, 4.39.
4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-hydroxybutanenitrile (3d).
To a cooled (0°C) solution of 2 (2.00 mmol, 410 mg) in ethanol (15 mL) and acetic acid (3 mL),
was added an aqueous solution (10 mL) of sodium cyanide (3.00 mmol, 147 mg) and the
resulting mixture was stirred for 5 hours after removing of the cooling bath. After completion of
the reaction, the crude reaction mixture was extracted with ethyl acetate (2 x 20 mL), and the
organic phases were dried on anhydrous sodium sulfate and filtered. After removal of the
organic solvent and subsequent purification by flash chromatography (petroleum ether – ethyl
acetate, 1:1) compound 3d was obtained as a white solid (419 mg, 91% yield), mp 104°C (lit.,2
104°C).
IR (NaCl) 3469, 2931, 2246, 2201, 1718, 1690, 716 cm-1.
1H NMR (250 MHz, CDCl3) 2.58 (m, 2H), 3.21 (bs, 1H), 3.89 (dd, J = 5.3 Hz, J = 10.1 Hz, 2H),
4.21 (m, 1H), 7.73-7.91 (m, 4H).
13C NMR (62.5 MHz, CDCl3) δ 23.7, 43.1, 66.6, 116.8, 123.8, 131.2, 134.5, 168.8.
Anal. Calcd. for C12H10N2O3: C, 62.60; H, 4.38; N, 12.17. Found: C, 62.31; H, 4.49; N, 12.33.
2-(3-azido-2-hydroxypropyl)-1H-isoindole-1,3(2H)-dione (3e).
To an aqueous solution of sodium azide (845 mg, 13.00 mmol, 13 mL) cooled at 0°C, were
added 2 (508 mg, 2.30 mmol) and acetic acid (2.3 mL). The mixture was stirred at 30°C for 6
hours and then was washed with saturated (aq) NaHCO3 and extracted with dichloromethane (2
x 30 mL). Organic phases were dried on anhydrous sodium sulfate, filtered and after removal of

the organic solvents in vacuo, compound 3e was obtained as a white solid (549 mg, 97% yield),
mp 65°C (lit.,3 64-66°C)
IR (NaCl) 3330, 2190, 2100, 1770, 900, 721 cm-1.
1H NMR (250 MHz, CDCl3) δ 2.99 (bs, 1H), 3.43 (m, 2H), 3.85 (m, 2H), 4.10 (m, 1H), 7.70-
7.93 (m, 4H).
13C NMR (62.5 MHz, CDCl3) δ 41.5, 54.6, 69.0, 123.2, 131.9, 134.3, 168.8.
Anal. Calcd. for C11H10N4O3: C, 53.66; H, 4.09; N, 22.75. Found: C, 53.88; H, 4.21; N, 22.91.
2-(3-fluoro-2-hydroxypropyl)-1H-isoindole-1,3(2H)-dione (3f).
To a solution of 2,3-epoxypropylphthalimide (2) (4.00 mmol, 820 mg) in toluene (15 mL) were
added ammonium hydrogen sulfate (0.80 mmol, 92 mg), 18-crown-6 (500 mg), potassium
hydrogen difluoride (8.00 mmol, 825 mg) and the resulting mixture was heated at 120°C during
18 h. After cooling, the crude was diluted with ethyl acetate (20 mL), washed with brine (15
mL) and extracted with ethyl acetate (4 x 15 mL). The organic phase was dried on anhydrous
sodium sulfate, filtered and after removal of the organic solvent in vacuo and subsequent
purification by flash chromatography (silica gel, ethyl acetate : petroleum ether, 7/3) pure
compound 3f (696 mg, 78% yield) was obtained as a white solid (mp, 91°C, lit.,4 91-93°C).
IR (NaCl) 3330, 1770, 901, 720, 651 cm-1.
1H NMR (250 MHz, CDCl3) 2.93 (bs, 1H), 3.88-3.95 (m, 2H), 4.09-4.18 (m, 1H), 4.43 (m, 1H),
4.55 (m, 1H), 7.75 (dd, J = 3.0 Hz, J = 5.3 Hz), 7.88 (dd, J = 3.0 Hz, J = 5.3 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 40.6 (d, 3J = 7.1 Hz), 68.9 (d, 2J = 20.5 Hz), 84.2 (d, 1J = 70.4
Hz), 123.7, 131.8, 134.3, 168.7.
19F NMR (235 MHz, CDCl3) δ -170.8.
Anal. Calcd. for C11H10FNO3: C, 59.19; H, 4.52; N, 6.28. Found: C, 59.42; H, 4.71; N, 6.40.
2-[2-hydroxy-3-(phenylthio)propyl]-1H-isoindole-1,3(2H)-dione (3g).
To a chloroform (20 mL) solution of 2 (4.00 mmol, 820 mg) were added zinc (II) perchlorate
hexahydrate (20 mol %, 0.80 mmol, 298 mg) and thiophenol (4.00 mmol, 441 mg, 0.41 mL).
The mixture was stirred at rt for 6 hours and then washed with water and extracted with
dichloromethane (2 x 20 mL). After drying over anhydrous sodium sulfate, filtration and
removal of the solvent in vacuo, the crude reaction product was purified by flash

chromatography (petroleum ether – ethyl acetate, 8:2), affording 3g (1139 mg, 91% yield) as a
light yellow solid (mp 37°C, lit.,2 38-40°C).
IR (NaCl) 3454, 1771, 1709, 1468, 1374, 1313, 1167, 904, 725, 684 cm-1.
1H NMR (250 MHz, CDCl3) 2.90 (dd, J = 8.3 Hz, J = 16.3 Hz, 2H), 3.90-4.12 (m, 3H), 7.07-
7.91 (m, 9H).
13C NMR (62.5 MHz, CDCl3) δ 39.5, 42.9, 68.9, 123.2, 123.7, 124.0, 126.9, 129.2, 130.5,
132.1, 132.5, 134.2, 134.3, 134.5, 135.0, 168.2.
Anal. Calcd. for C17H15NO3S: C, 65.16; H, 4.82; N, 4.47; S, 10.23. Found: C, 65.39; H, 4.99; N,
4.62; S, 10.09.
2-{2-hydroxy-3-[methyl(phenyl)amino]propyl}-1H isoindole-1,3(2H)-dione (3h).
To a chloroform (20 mL) solution of 1 (4.00 mmol, 820 mg) were added zinc (II) perchlorate
hexahydrate (20 mol %, 0.80 mmol, 298 mg) and N-methylaniline (4.00 mmol, 429 mg, 0.43
mL). The mixture was stirred at rt for 4 hours and then washed with water and extracted with
dichloromethane (2 x 20 mL). After drying over anhydrous sodium sulfate, filtration and
removal of the solvent in vacuo, the crude reaction product was purified by flash
chromatography (petroleum ether – ethyl acetate, 8:2), affording 3h (1092 mg, 88% yield) as a
yellow solid (mp 75-76°C).
IR (NaCl) 3464, 3070, 1770, 1713, 1392, 1040, 912, 722 cm-1.
1H NMR (250 MHz, CDCl3) 2.77 (bs, 1H), 3.00 (s, 3H), 3.53 (m, 2H), 3.95 (m, 2H), 4.25 (m,
1H), 6.74-6.84 (m, 3H), 7.23 (m, 2H), 7.71-7.89 (m, 4H).
13C NMR (62.5 MHz, CDCl3) δ 36.4, 42.2, 68.3, 69.3, 113.5, 123.5, 123.6, 129.3, 131.9, 134.2,
134.3, 149.9, 168.7.
Anal. Calcd. for C18H18N2O3: C, 69.66; H, 5.85; N, 9.03. Found: C, 69.91; H, 6.01; N, 8.88.

Dess-Martin oxidation of aminoalcohols 3a-h. (General Procedure B)
To a solution of alcohol (1.00 equiv.) in dichloromethane (10 mL) at room temperature, Dess-
Martin Periodinane (1.20 equiv.) was added and the mixture was stirred at the same temperature
for the appropriate time (Table 2). Then, diethyl ether (20 mL) and a saturated aqueous solution
of sodium thiosulfate (15 mL) followed by addition of saturated solution of sodium bicarbonate
were added and the resulting mixture was stirred for 5 min. The organic phase was separated,
dried under sodium sulphate, filtered and concentrated.
2-(3-chloro-2-oxopropyl)-1H-isoindole-1,3(2H)-dione (4a).
By following the General Procedure B, starting from 479 mg of 3a (2.00 mmol) and 1018 mg
(2.40 mmol) of DMP, ketone 4a was obtained in 97% yield (461 mg) as a white solid (mp
122°C, lit.,1 122°C).
IR (NaCl) 1772, 1732, 1718 cm-1.
1H NMR (250 MHz, CDCl3) δ 4.20 (s, 2H), 4.75 (s, 2H), 7.80 (dd, J = 3.0 Hz, J = 5.1 Hz, 2H),
7.94 (dd, J = 3.0 Hz, J = 5.1 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 44.7, 46.2, 123.7, 132.6, 134.3, 167.4, 195.5.
Anal. Calcd. for C11H8ClNO3: C, 55.60; H, 3.39; N, 5.89. Found: C, 55.79; H, 3.52; N, 6.09.
2-(3-bromo-2-oxopropyl)-1H-isoindole-1,3(2H)-dione (4b).
By following the General Procedure B, starting from 568 mg of 3b (2.00 mmol) and 1018 mg
(2.40 mmol) of DMP, ketone 4b was obtained in 99% yield (558 mg) as a white solid (mp
147°C, lit.,5 147-148°C).
IR (NaCl) 1773, 1732, 1719 cm-1.
1H NMR (250 MHz, CDCl3) δ 4.03 (s, 2H), 4.80 (s, 2H), 7.76 (dd, J = 3.0 Hz, J = 5.2 Hz, 2H),
7.94 (dd, J = 3.0 Hz, J = 5.2 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 35.1, 45.8, 123.1, 132.9, 134.5, 167.8, 196.8.
Anal. Calcd. for C11H8BrNO3: C, 46.84; H, 2.86; N, 4.97. Found: C, 47.08; H, 2.97; N, 5.08.

2-(3-iodo-2-oxopropyl)-1H-isoindole-1,3(2H)-dione (4c).
By following the General Procedure B, starting from 662 mg of 3c (2.00 mmol) and 1018 mg
(2.40 mmol) of DMP, ketone 4c was obtained in 94% yield (619 mg) as a yellow solid (mp
182°C, lit.,1 182-185°C).
IR (NaCl) 1774, 1730, 1721 cm-1.
1H NMR (250 MHz, CDCl3) δ 3.96 (s, 2H), 4.82 (s, 2H), 7.76 (dd, J = 3.0 Hz, J = 5.4 Hz, 2H),
7.90 (dd, J = 3.0 Hz, J = 5.4 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 1.2, 43.4, 123.7, 132.0, 134.3, 167.5, 195.4.
Anal. Calcd. for C11H8INO3: C, 40.15; H, 2.45; N, 4.26. Found: C, 40.34; H, 2.59; N, 4.41.
4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanenitrile (4d).
By following the General Procedure B, starting from 460 mg of 3d (2.00 mmol) and 1018 mg
(2.40 mmol) of DMP, ketone 4d was obtained in 95% yield (433 mg) as a light yellow syrup.
IR (NaCl) 2201, 2130, 1770, 1733, 1722 cm-1.
1H NMR (250 MHz, CDCl3) δ 3.59 (s, 2H), 4.74 (s, 2H), 7.80 (dd, J = 3.0 Hz, J = 5.1 Hz, 2H),
7.87 (dd, J = 3.0 Hz, J = 5.1 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 39.2, 42.6, 113.6, 123.5, 131.8, 134.1, 167.2, 195.8.
Anal. Calcd. for C12H8N2O3: C, 63.16; H, 3.53; N, 12.28. Found: C, 63.34; H, 3.68; N, 12.45.
2-(3-azido-2-oxopropyl)-1H-isoindole-1,3(2H)-dione (4e).
By following the General Procedure B, starting from 492 mg of 3e (2.00 mmol) and 1018 mg
(2.40 mmol) of DMP, ketone 4e was obtained in 98% yield (479 mg) as a white solid (mp
125°C, lit.,6 124-126°C).
IR (NaCl) 3328, 2190, 2101, 1774, 1736, 1715 cm-1.
1H NMR (250 MHz, CDCl3) δ 4.16 (s, 2H), 4.60 (s, 2H), 7.76 (dd, J = 3.1 Hz, J = 5.2 Hz, 2H),
7.88 (dd, J = 3.1 Hz, J = 5.2 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 44.1, 45.5, 123.7, 131.6, 134.1, 168.9, 196.9.
Anal. Calcd. for C11H8N4O3: C, 54.10; H, 3.30; N, 22.94. Found: C, 53.88; H, 3.48; N, 22.51.

2-(3-fluoro-2-oxopropyl)-1H-isoindole-1,3(2H)-dione (4f)
By following the General Procedure B, starting from 446 mg of 3f (2.00 mmol) and 1018 mg
(2.40 mmol) of DMP, ketone 4f was obtained in 91% yield (402 mg) as a white solid after
purification by flash chromatography on silica gel (petroleum ether/ ethyl acetate, 7:3).
IR (NaCl) 1770, 1729, 1713 cm-1.
1H NMR (250 MHz, CDCl3) δ 4.68 (s, 2H), 4.99 (d, 2J = 47.5 Hz, 2H), 7.71 (dd, J = 3.0 Hz, J =
5.3 Hz, 2H), 7.81 (dd, J = 3.0 Hz, J = 5.3 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 44.5, 85.1 (d, 1J = 182.6 Hz), 123.7, 131.9, 134.5, 167.6, 199.0.
19F NMR (235 MHz, CDCl3) δ -169.6.
Anal. Calcd. for C11H8FNO3: C, 59.73; H, 3.65; N, 6.33. Found: C, 59.52; H, 3.86; N, 6.49.
2-[2-oxo-3-(phenylthio)propyl]-1H-isoindole-1,3(2H)-dione (4g)
By following the General Procedure B, starting from 627 mg of 3g (2.00 mmol) and 1018 mg
(2.40 mmol) of DMP, ketone 4g was obtained in 92% yield (573 mg) as a thick oil after
purification by flash chromatography on silica gel (petroleum ether/ ethyl acetate, 8:2).
IR (NaCl) 1772, 1736, 1719 cm-1.
1H NMR (250 MHz, CDCl3) δ 3.71 (s, 2H), 4.67 (s, 2H), 7.19-7.41 (m, 5H), 7.66 (dd, J = 2.8
Hz, J = 4.9 Hz, 2H), 7.79 (dd, J = 2.8 Hz, J = 4.9 Hz, 2H).
13C NMR (62.5 MHz, CDCl3) δ 42.1, 44.7, 123.5, 127.5, 129.1, 130.4, 131.9, 133.6, 134.5,
167.5, 197.5.
Anal. Calcd. for C17H13NO3S: C, 65.58; H, 4.21; N, 4.50; S, 10.30. Found: C, 65.80; H, 4.39; N,
4.31; S, 10.12.
2-{3-[methyl(phenyl)amino]-2-oxopropyl}-1H-isoindole-1,3(2H)-dione (4h)
By following the General Procedure B, starting from 621 mg of 3f (2.00 mmol) and 1018 mg
(2.40 mmol) of DMP, ketone 4f was obtained in 86% yield (530 mg) as a yellow thick oil after
purification by flash chromatography on silica gel (petroleum ether/ ethyl acetate, 9:1).
IR (NaCl) 2987, 1775, 1732, 1714 cm-1.
1H NMR (250 MHz, CDCl3) δ 3.08 (s, 3H), 3.96 (s, 2H), 4.72 (s, 2H), 6.61-6.76 (m, 3H), 7.18
(m, 2H), 7.69 (dd, J = 3.0 Hz, J = 4.9 Hz, 2H), 7.79 (dd, J = 3.0 Hz, J = 4.9 Hz, 2H).

13C NMR (62.5 MHz, CDCl3) δ 32.1, 44.9, 60.4, 112.5, 122.4, 123.7, 129.6, 132.0, 133.8,
148.6, 167.6, 194.7.
Anal. Calcd. for C18H16N2O3: C, 70.12; H, 5.23; N, 9.09. Found: C, 69.91; H, 5.46; N, 9.19.
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-hydroxypropyl]acetamide (5)
To a solution of azidoalcohol 3e (320 mg, 1.30 mmol) in chloroform (10 mL) were added 2,6-
lutidine (181 mg, 0.20 mL, 1.69 mmol) and thioacetic acid (129 mg, 0.12 mL, 1.69 mmol) and
the resulting solution was stirred at 60°C during 6 hours. After cooling at rt, a solution of
saturated sodium bicarbonate was added (15 mL) and then the mixture was extracted with
dichloromethane (3 x 15 mL). After drying the organic phase over anhydrous sodium sulfate,
filtration and removal of the solvent in vacuo, the crude reaction product was purified by flash
chromatography (petroleum ether – ethyl acetate, 8:2), affording 5 (286 mg, 84% yield) as a
yellow thick oil.
IR (NaCl) 3450, 2980, 1775, 1698 cm-1.
1H NMR (250 MHz, CDCl3) δ 1.83 (s, 3H), 2.96 (s, 1H), 3.20-3.45 (m, 2H), 3.66-3.83 (m, 2H),
4.30 (m, 1H), 7.61 (dd, J = 3.0 Hz, J = 5.0 Hz, 2H), 7.68 (dd, J = 3.0 Hz, J = 5.0 Hz, 2H), 7.96
(s, 1H).
13C NMR (62.5 MHz, CDCl3) δ 21.7, 44.8, 53.8, 68.7, 123.1, 131.8, 134.2, 168.7, 175.0.
Anal. Calcd. for C13H14N2O4: C, 59.54; H, 5.38; N, 10.68. Found: C, 59.81; H, 5.53; N, 10.87.
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-oxopropyl]acetamide (6)
By following the General Procedure B, starting from 200 mg of 5 (0.76 mmol) and 388 mg
(0.91 mmol) of DMP, ketone 6 was obtained in 87% yield (172 mg) as a light yellow oil after
purification by flash chromatography on silica gel (petroleum ether/ ethl acetate, 8:2).
IR (NaCl) 1771, 1733, 1714, 1696 cm-1.
1H NMR (250 MHz, CDCl3) δ 1.83 (s, 3H), 4.41 (s, 2H), 4.73 (s, 2H), 7.72 (dd, J = 3.0 Hz, J =
5.1 Hz, 2H), 7.86 (dd, J = 3.0 Hz, J = 5.1 Hz, 2H), 8.02 (s, 1H).
13C NMR (62.5 MHz, CDCl3) δ 22.1, 46.8, 55.1, 123.6, 131.9, 134.1, 168.5, 169.9, 197.4.
Anal. Calcd. for C13H12N2O4: C, 60.00; H, 4.65; N, 10.76. Found: C, 60.23; H, 4.91; N, 10.90.

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