Potassium Carbonate → 2-(1',2'-Dihydro-2'-oxospiro[cyclohexane-1.3'-[3H]indol]-5'-yl)-1H-pyrrole-1-carboxylic acid, tert-butyl ester

HRID 1760291Notes

Reaction equation

HRID 1760291 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[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.B([C:20]1[N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:22]=[CH:23][CH:24]=1)(O)O.C([O-])([O-])=O.[K+].[K+]>O>[O:11]=[C:6]1[C:5]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:20]3[N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:22]=[CH:23][CH:24]=3)[CH:3]=2)[NH:7]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 114714965'-Bromo-1',2'-dihydrospiro[cyclohexane-1,3'-indole]-2'-one

Product 1

HCID 120449712-(1',2'-Dihydro-2'-oxospiro[cyclohexane-1.3'-[3H]indol]-5'-yl)-1H-pyrrole-1-carboxylic acid, tert-butyl esterYield 77.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 5′-bromo-spiro[cyclohexane-1,3′-indolin]-2′-one (3.4 g, 12 mmol) in 1,2-DME (100 mL) under a nitrogen atmosphere was added tetrakis(triphenylphospine)palladium(0) (70 mg, 5 mol %). After 15 min, 2-borono-1H-pyrrole-1-carboxylic acid, 1-tert butyl ester (1.3 eq, 3.31 g, 15.6 mmol) and a solution of K2CO3 (2.3 eq, 3.83 g, 27.6 mmol) in water (5 mL) were added sequentially. The solution was heated to 80° C. for 3 h and allowed to cool. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (2×100 mL). The organic layers were combined, washed with brine (150 mL) and dried over MgSO4. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with 30% EtOAc/hexane) to give 2-(1′,2′-dihydro-2′-oxospiro[cyclohexane-1,3′-[3H]indol]-5′-yl)-1H-pyrrole-1-carboxylic acid, tert-butyl ester (3.4 g, 76%) as a white powder, mp 177° C. 1H NMR (CDCl3; 300 MHz) δ 1.38 (s, 9 H), 1.59-1.93 (m, 10 H), 6.18 (m, 1 H), 6.23 (‘t’, 1H, 3 Hz), 6.91 (d, 1 H, J=8 Hz), 7.21 (d, 1 H, J=8 Hz), 7.34 (m, 1 H), 7.44 (s, 1 H), 8.33 (br s, 1 H, D2Oex). MS ((+)-APCI) m/z 367 [(M+H)+]. Anal. Calcd for C22H26N2O3: C, 72.11; H, 7.15; N, 7.64. Found: C, 71.7; H, 7.16; N, 7.5.

Workup

  1. temperatureto cool
  2. extractionextracted with EtOAc (2×100 mL)
  3. washwashed with brine (150 mL)
  4. dry with materialdried over MgSO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (eluting with 30% EtOAc/hexane)

Sources & evidence

ORD record
ord-bf25ac1798d74d93ba0663151520fb48
Source dataset
uspto-grants-2005_01
Patent number
US06841568B2

Reaction notes

Loading…