Monobenzone → (R)-2-(4-Benzyloxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 750031Notes

Reaction equation

HRID 750031 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@@H:26]1[CH2:30]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:24])([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C>[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@@H:26]1[CH2:30][O:17][C:14]1[CH:13]=[CH:12][C:11]([O:10][CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)=[CH:16][CH:15]=1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 7638MonobenzoneHCID 24758Sodium hydrideHCID 11760051(R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 68999348(R)-2-(4-Benzyloxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 65.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 250 mL round bottomed flask which contained a suspension of NaH (1 g, 24 mmol) in DMF (100 mL) was added p-benzyloxy phenol (4 g, 20 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 (7.1 g, 20 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. for 5 h. After cooling to rt, the mixture was poured into 500 mL ice-water solution and this solution was allowed to stir at 0° C. for 30 min. The solid formed was filtered out, dried through air to provide the crude which was further purified by recrystallization with ether-hexane to afford the title product (5 g, 65%); LCMS; 100%, ESI+, Calcd: 383.49 m/z. Found: 284.4, (M+1-boc). 1H NMR (400 MHz, CDCl3); δ 1.47 (s, 9H), 1.79-2.10 (m, 4H), 3.26-3.45 (m, 2H), 3.66-3.91 (m, 1H), 4.01-4.19 (m 2H), 5.01 (s, 2H), 6.83-6.91 (m, 4H), 7.28-7.44 (m, 5H):

Workup

  1. customTo a 250 mL round bottomed flask which contained
  2. temperaturethen cooled to 0° C
  3. temperatureThe resulting mixture was allowed warm to rt
  4. stirringstir at rt for 30 min
  5. temperaturewas heated to 95° C. for 5 h
  6. temperatureAfter cooling to rt
  7. stirringto stir at 0° C. for 30 min
  8. customThe solid formed
  9. filtrationwas filtered out
  10. customdried through air
  11. customto provide the crude which
  12. customwas further purified by recrystallization with ether-hexane

Sources & evidence

ORD record
ord-a3c6535640aa48ccaaf400f47e55c4e9
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

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