Phthalimide → 2-(3-Bromo-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl)isoindoline-1,3-dione

HRID 2046538Notes

Reaction equation

HRID 2046538 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]2[CH:6](O)[CH2:7][CH2:8][C:9]=2[CH:10]=1.[C:12]1(=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](=[O:21])[NH:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]2[CH2:8][CH2:7][CH:6]([N:13]3[C:14](=[O:21])[C:15]4[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:12]3=[O:22])[C:5]2=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 468641543-bromo-5H,6H,7H-cyclopenta(b)pyridin-7-ol

Product 1

HCID 682968342-(3-Bromo-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(rac)-3-Bromo-6,7-dihydro-5H-[1]pyrindin-7-ol (4.84 g, 22.6 mmol) and isoindoline-1,3-dione (3.66 g, 24.9 mmol) were dissolved in THF (130 ml); then, triphenylphosphine (7.41 g, 28.3 mmol) was added, followed by a solution of di-tert-butyl azodicarboxylate (6.25 g, 27.1 mmol) in THF (3.0 ml) below 5° C.; stirring at RT was then continued for 20 hours. The reaction mixture was concentrated in vacuo to give a crude product (23.507 g), which was purified by flash chromatography (silica gel, 100 g, 10% to 50% EtOAc in heptane) to give 2-((rac)-3-bromo-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl)isoindoline-1,3-dione (11.114 g, not pure). This intermediate was dissolved in ethanol (140 ml), then, while stirring, hydrazine hydrate (3.01 g, 2.95 ml, 75.1 mmol) was added and the reaction mixture was heated up to reflux. After 2 hours, it was poured into NaOH 1N (150 ml) and extracted with CH2Cl2 (2×100 ml). The organic layers were dried over MgSO4, filtered and concentrated in vacuo to give a crude product (8.845 g) which was purified by flash chromatography (silica gel, 100 g, 0% to 20% MeOH in CH2Cl2) to yield the title compound (1.80 g, 37%) as purple oil. MS: 213.0 (MH+, 1Br).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto give a crude product (23.507 g), which
  3. customwas purified by flash chromatography (silica gel, 100 g, 10% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-78e5baba757d48ea95e9e413f9844a7a
Source dataset
uspto-grants-2013_11
Patent number
US08592426B2

Reaction notes

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