N-Hydroxyphthalimide → Benzyl 5-[3-(1,3-dioxoisoindolin-2-yloxy)propoxy]-3-chlorobenzoate

HRID 1698860Notes

Reaction equation

HRID 1698860 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([O:18][CH2:19][CH2:20][CH2:21][OH:22])[CH:17]=1)[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[N:43]1[C:47](=[O:48])[C:46]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:45]2[C:44]1=[O:53].N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[O:53]=[C:44]1[C:45]2[C:46](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:47](=[O:48])[N:43]1[O:22][CH2:21][CH2:20][CH2:19][O:18][C:16]1[CH:17]=[C:2]([Cl:1])[CH:3]=[C:4]([CH:15]=1)[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6]

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 18322176Benzyl 3-chloro-5-(3-hydroxypropoxy)benzoate

Product 1

HCID 18322169Benzyl 5-[3-(1,3-dioxoisoindolin-2-yloxy)propoxy]-3-chlorobenzoateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of alcohol 26 (5.96 g, 18.6 mmol), triphenylphosphine (5.40 g, 20.5 mmol), and N-hydroxyphthalirnide (2.10 g, 20.5 mmol) in tetrahydrofuran (186 mL) was cooled to 0° C. and reacted slowly with diethyl azodicarboxylate (3.50 mL, 22.3 mmol). After warming to ambient temperature and stirring 16 hrs, the reaction was concentrated in vacuo and purified by chromatography on silica gel (10% ethyl acetate in hexanes) giving product 27 (5.18 g, 60%). 1H NMR (300 MHz, CDCl3) δ 7.83 (dd, 2H, J=5.6 Hz, 3.1 Hz), 7.75 (dd, 2H, J=5.6 Hz, 3.1 Hz), 7.63 (t, 1H, J=1.5 Hz), 7.51 (dd, 1H, J=2.4 Hz, 1.4 Hz), 7.40 (m, 5H), 7.12 (t, 1H, J=2.3 Hz), 5.35 (s, 2H), 4.41 (t, 2H, J=6.1 Hz), 4.28 (t, 2H, J=6.1 Hz), 2.25 (pentet, 2H, J=6.1 Hz).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. custompurified by chromatography on silica gel (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8250fae45fd7470892bbf7e209111e20
Source dataset
uspto-grants-2002_02
Patent number
US06344466B2

Reaction notes

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