Potassium Carbonate → (R)-2-[4-(4-Thiophen-3-yl-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 750066Notes

Reaction equation

HRID 750066 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:30]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([C:32]3[CH:33]=[CH:34][S:30][CH:31]=3)=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 581760Thiophene-3-boronic acidHCID 44221510(R)-2-[4-(4-Iodo-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68999764(R)-2-[4-(4-Thiophen-3-yl-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a 25 mL press resistant vial which contained a suspension of (R)-2-[4-(4-Iodo-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (250 mg, 0.5 mmol), thiophene-3-boronic acid (130 mg, 1 mmol), palladium(II) acetate (20 mg, 0.1 mmol) and triphenyl phosphine (60 mg, 0.25 mmol) in DME (10 mL) was added potassium carbonate (500 mg, 3 mmol), ethanol (1 mL) and water (1 mL) at rt. The tube was sealed and the mixture was allowed to stir at rt for 30 min and then was heated to 98° C. and stirred at 98° C. for 16 h. After cooling to rt, the mixture was poured onto 200 mL ice-water solution and then extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×30 mL) and brine (20 mL). and dried over anhy. Na2SO4. The solvent was removed in vacuo to obtain the crude product which was purified by silica gel flash chromatography to afford title product, (130 mg, 60%); 1H NMR (400 MHz, CDCl3); δ 1.48 (s, 9H), 1.81-2.10 (m, 4H), 3.30-3.48 (m, 2H), 3.87-4.10 (m, 1H), 4.10-4.30 (m, 2H), 6.98-7. (m, 2H), 7.42-7.48 (m, 2H), 7.58-7.60 (m, 1H), 7.70 (d, J=8.4 Hz, 2H), 7.80-7.84 (m, 4H):

Workup

  1. customThe tube was sealed
  2. temperaturewas heated to 98° C.
  3. stirringstirred at 98° C. for 16 h
  4. temperatureAfter cooling to rt
  5. extractionextracted with EtOAc (3×30 mL)
  6. washThe combined organic layers were washed with water (2×30 mL) and brine (20 mL)
  7. customand dried over anhy
  8. customThe solvent was removed in vacuo
  9. customto obtain the crude product which
  10. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-bc8e7491f38b4146996ca8c4b5e9b3de
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

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