Potassium Carbonate → 2-(1', 2'-dihydro-2'-oxospiro[cyclopentane-1,3'-[3H]indol]-5'-yl)-1H pyrrole-1-carboxylic acid, tert-butyl ester

HRID 276987Notes

Reaction equation

HRID 276987 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]12[CH2:15][CH2:14][CH2:13][CH2:12]1.[C:16]([O:20][C:21]([N:23]1[CH:27]=[CH:26][CH:25]=[C:24]1B(O)O)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:11]=[C:6]1[C:5]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:24]3[N:23]([C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[CH:27]=[CH:26][CH:25]=3)[CH:3]=2)[NH:7]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 120449735'-Bromo-1',2'-dihydrospiro[cyclopentane-1,3'-indole]-2'-one

Product 1

HCID 120449742-(1', 2'-dihydro-2'-oxospiro[cyclopentane-1,3'-[3H]indol]-5'-yl)-1H pyrrole-1-carboxylic acid, tert-butyl esterYield 83.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 5′-bromospiro[cyclopentane-1,3′-[3H]indol]-2′(1′H)-one 2.0 g, 7.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (430 mg, 0.3 mmol) in ethylene glycol dimethyl ether (50 mL) was stirred under a flow of nitrogen for 15 min. To the solution was added sequentially 1-t-butoxycarbonylpyrrole-2-boronic acid (2.1 g, 9.7 mmol) and potassium carbonate (2.4 g, 17 mmol) in water (10 mL). The mixture was heated to 80° C. for 3 h and allowed to cool. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were combined, washed with brine (30 mL) and dried over magnesium sulfate. The solution was filtered and concentrated in vacuo. Crystallization from 20% ethyl acetate/hexane gave 2-(1′, 2′-dihydro-2′-oxospiro[cyclopentane-1,3′-[3H]indol]-5′-yl)-1H pyrrole-1-carboxylic acid, tert-butyl ester (2.2 g, 83%) as a white powder, mp 179-180.5° C. 1H NMR (DMSO-d6, 400 MHz) δ 1.30 (s, 9H), 1.75-1.98 (m, 8 H), 6.16 (dd, 1 H, J=1.8, 3.3 Hz), 6.22 (‘t’, 1 H, J=3.3, 3.3 Hz), 6.79 (d, 1 H, J=7.9 Hz), 7.08 (dd, 1 H, J=1.8, 7.9 Hz), 7.14 (‘d’, 1 H, J=1.5 Hz), 7.28 (dd, J=1.9, 3.3 Hz), 10.30 (s, 1 H). MS (EI) m/z 352 [M+]. Anal. Calcd for C21H24N2O3: C, 71.57; H, 6.86; N, 7.95. Found: C, 71.08; H, 6.83; N, 7.74.

Workup

  1. temperatureto cool
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washwashed with brine (30 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customCrystallization from 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-572ff4797ab54e0780b96a1eae972176
Source dataset
uspto-grants-2002_03
Patent number
US06355648B1

Reaction notes

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