5-Bromo-2-chloroanisole → Tert-butyl 2-(4-chloro-3-methoxyphenyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate

HRID 700

Reaction equation

HRID 700 reaction equation
CC(C)(C)OC(=O)N1CC2CNCC2C1.COc1cc(Br)ccc1Cl>CC(C)(C)[O-].Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>COc1cc(N2CC3CN(C(=O)OC(C)(C)C)CC3C2)ccc1Cl

Participants

7

Reactant 2

HCID 27695675-Bromo-2-chloroanisoleHCID 4142526Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylate

Product 1

HCID 59813953Tert-butyl 2-(4-chloro-3-methoxyphenyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylateYield 64.57%

Reagents, catalysts & solvents 4

HCID 23676156Sodium t-butoxideReagentHCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (205 mg, 0.97 mmol), 5-Bromo-2-chloroanisole (235 mg, 1.06 mmol), Sodium tert- butoxide (130 mg, 1.35 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (30.1 mg, 0.05 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (44.2 mg, 0.05 mmol) in toluene (10 mL) under a nitrogen atmosphere was stirred at 90 °C for 12h. The solution was washed with saturated NaHCO3 solution, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was loaded on a 24g silica gel column and purified on a Teledyne Isco instrument, eluting with 20% to 40% ethyl acetate in heptane to provide tert-butyl 5-(4-chloro-3-methoxyphenyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (220 mg, 64.6 %) as a solid. Used directly for the next step. MS m/z 353.3 [M+H]+ (ESI)

Sources & evidence

ORD record
ord-b0d4d24d68264e0ba39e9d5692455d36
Source dataset
750 AstraZeneca ELN dataset
Original link
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Linked notes

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