Sodium hydride → (S)-2-(4-p-Tolyloxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 749967Notes

Reaction equation

HRID 749967 reaction equation
[C:1]1([CH3:15])[CH:6]=[CH:5][C:4]([O:7][C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:3][CH:2]=1.[H-].[Na+].[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)C=O>[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[CH2:30][O:14][C:11]1[CH:12]=[CH:13][C:8]([O:7][C:4]2[CH:3]=[CH:2][C:1]([CH3:15])=[CH:6][CH:5]=2)=[CH:9][CH:10]=1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6414404-(4-Methylphenoxy)phenolHCID 11783214tert-Butyl (2S)-2-(((4-methylbenzene-1-sulfonyl)oxy)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 68999151(S)-2-(4-p-Tolyloxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

4-p-Tolyloxy-phenol (2 g, 9.98 mmol) was taken into anhydrous dimethylformamide (40 mL) and cooled to 0° C. A 60% dispersion of Sodium hydride (0.52 g, 13 mmol) was added portionwise over 10 min. The reaction was kept at 0° C. for 45 min. and then heated to 35° C. for 15 min. (S)-2-(Toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (4.26 g, 11.9 mmol) was taken into anhydrous dimethylformamide (20 mL) and added to the reaction dropwise over 5 min. The reaction was heated at 75° C. for 12 h. The reaction was quenched with water under nitrogen atmosphere. The mixture was extracted with ethyl acetate (3×). The ethyl acetate was washed with brine, dried over sodium sulfate, and concentrated to dryness. The crude product was purified by flash chromatography (20:1 silica ratio, eluted with 10% ethyl acetate in hexane) to obtain the title product (3.02 g, 7.88 mmol, 79% yield); MS; m/z 383. found 384 (M+H); 1H NMR (400 MHz, DMSO-d6) δ 1.40 (s, 9H), 1.80 (s, 1H), 1.89-1.92 (m, 3H), 2.26 (s, 3H), 3.27 (s, 2H), 3.86 (s, 1H), 4.00-4.06 (m, 2H), 6.81-6.83 (m, 2H), 6.91-6.98 (m, 4H), 7.13-7.15 (m, 2H).

Workup

  1. additionadded to the reaction dropwise over 5 min
  2. temperatureThe reaction was heated at 75° C. for 12 h
  3. customThe reaction was quenched with water under nitrogen atmosphere
  4. extractionThe mixture was extracted with ethyl acetate (3×)
  5. washThe ethyl acetate was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by flash chromatography (20:1 silica ratio, eluted with 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-af09aa427d6a492798ae0ac87b182d33
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

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