1,3-Dibromobenzene → Methyl 6-(3-bromophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601909Notes

Reaction equation

HRID 601909 reaction equation
O=C1C2NC(C(OC)=O)=CC=2CC1.[Br:14][C:15]1[CH:16]=[C:17]([Mg:21][Br:22])[CH:18]=[CH:19][CH:20]=1.[Br:23][C:24]1[CH:25]=[C:26]([C:30]2(O)[C:34]3[NH:35][C:36]([C:38]([O:40][CH3:41])=[O:39])=[CH:37][C:33]=3[CH2:32][CH2:31]2)[CH:27]=[CH:28][CH:29]=1.[Mg].BrC1C=CC=C(Br)C=1.C1(CC2C3C=C(C(O)=O)NC=3CC2)CCCCC1>C1COCC1.CO>[Br:23][C:24]1[CH:25]=[C:26]([CH:30]2[C:34]3[NH:35][C:36]([C:38]([O:40][CH3:41])=[O:39])=[CH:37][C:33]=3[CH2:32][CH2:31]2)[CH:27]=[CH:28][CH:29]=1.[Br:14][C:15]1[CH:16]=[C:17]([Mg:21][Br:22])[CH:18]=[CH:19][CH:20]=1

Participants

10

Reactant 6

HCID 79271,3-DibromobenzeneHCID 5462224MagnesiumHCID 441251164-(Cyclohexylmethyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acidHCID 59180137Methyl 6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 66873783Methyl 6-(3-bromophenyl)-6-hydroxy-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate2×HCID 178419620HCID 178419620, compound

Product 2

HCID 59180226Methyl 6-(3-bromophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 178419620HCID 178419620, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

The title compound was synthesized in two steps. First, methyl 6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.503 g, 2.81 mmol) and (3-bromophenyl)magnesium bromide (synthesized in situ) were reacted according to General Procedure 3 to give the carbinol-containing compound methyl 6-(3-bromophenyl)-6-hydroxy-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate. (Note: (3-Bromophenyl)magnesium bromide was synthesized as follows: Activated magnesium (0.308 g, 12.67 mmol) was placed in a flask and anhydrous THF (50 mL) was added. 1,3-dibromobenzene (1.6 mL, 13.2 mmol) and a catalytic amount of 12 was added. The solution was stirred gently at ambient temperature for 30 min. Additional anhydrous THF (25 mL) was added and the solution refluxed for 3 h, and then allowed to cool to ambient temperature). Methyl 6-(3-bromophenyl)-6-hydroxy-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate was hydrogenated according to General Procedure 6 (with Pt2O), and was purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-30% EtOAc/heptane affording the product as a slightly yellow solid: 0.213 g (83% yield). 1H NMR (400 MHz, ACETONE-d6) δ ppm 2.27 (ddt, J=13.19, 8.32, 5.23, 5.23 Hz, 1H), 2.58-2.67 (m, 1H), 2.71-2.79 (m, 1H), 2.90-3.01 (m, 1H), 3.73 (s, 3H), 4.30 (dd, J=8.64, 5.17 Hz, 1H), 6.62-6.65 (m, 1H), 7.10-7.14 (m, 1H), 7.21-7.26 (m, 1H), 7.28-7.30 (m, 1H), 7.35-7.40 (m, 1H), 10.67 (br. s, 1H); LCMS (ESI+) 344.0 (M+Na).

Workup

  1. temperaturethe solution refluxed for 3 h
  2. temperatureto cool to ambient temperature)
  3. customwas purified by column chromatography (Isco CombiFlash)
  4. washeluting with a gradient of 0-30% EtOAc/heptane affording the product as a slightly yellow solid

Sources & evidence

ORD record
ord-c7c4b817f36543b5b5289a356562fd62
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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