Sodium hydride → (R)-2-[4-(4-Iodo-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 750064Notes

Reaction equation

HRID 750064 reaction equation
[H-].[Na+].[I:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[O:11])=[CH:6][CH:5]=1.[C:19]([O:23][C:24]([N:26]1[CH2:30][CH2:29][CH2:28][C@@H:27]1[CH2:31]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:25])([CH3:22])([CH3:21])[CH3:20]>CN(C=O)C>[C:19]([O:23][C:24]([N:26]1[CH2:30][CH2:29][CH2:28][C@@H:27]1[CH2:31][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:10](=[O:11])[C:7]2[CH:8]=[CH:9][C:4]([I:3])=[CH:5][CH:6]=2)=[CH:13][CH:14]=1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11760051(R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylateHCID 13453359(4-Hydroxyphenyl)(4-iodophenyl)methanone

Product 1

HCID 44221510(R)-2-[4-(4-Iodo-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 25 mL vial which contained a suspension of NaH (60% in mineral oil, 60 mg, 1.5 mmol) in DMF (10 mL) was added the product from step 1 (324 mg, 1 mmol) at 0° C. The mixture was allowed to warm to rt and stir at rt for 30 min then cooled to 0° C. To this reaction mixture was added (R)-2-(toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (400 mg, 1.1 mmol) at 0° C. The resulting mixture was allowed warm to rt and stir at rt for 30 min and then was heated to 95° C. and stirred at 95° C. for 16 h. After cooling to rt, the mixture was poured onto 100 mL ice-water solution and this solution was allowed to stir at 0° C. for 30 min. The solid which formed was filtered out, dried through air to afford the title product (280 mg, 60%); 1H NMR (400 MHz, CDCl3); δ 1.47 (s, 9H), 1.82-2.11 (m, 4H), 3.30-3.48 (m, 2H), 3.85-4.05 (m, 1H), 4.07-4.30 (m, 2H), 6.96-7.25 (m, 2H), 7.47 (d, J=8.4 Hz, 2H), 7.77 (d, J=8.8 Hz, 2H), 7.83 (d, J=8.4 Hz, 2H):

Workup

  1. temperaturethen cooled to 0° C
  2. temperatureThe resulting mixture was allowed warm to rt
  3. stirringstir at rt for 30 min
  4. temperaturewas heated to 95° C.
  5. stirringstirred at 95° C. for 16 h
  6. temperatureAfter cooling to rt
  7. stirringto stir at 0° C. for 30 min
  8. customThe solid which formed
  9. filtrationwas filtered out
  10. customdried through air

Sources & evidence

ORD record
ord-2a27017bd33d4a8a99f29b75328b423f
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

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