Sodium hydride → (S)-N-Boc-2-[4-(4-trifluoromethyl-phenoxy)-phenoxymethyl]-pyrrolidine

HRID 1909643Notes

Reaction equation

HRID 1909643 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:22]=[CH:21][C:6]([O:7][C:8]2[CH:20]=[CH:19][C:11]([O:12][CH2:13][C@@H:14]3[CH2:18][CH2:17][CH2:16][NH:15]3)=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.FC(F)(F)C1C=CC(OC2C=CC(O)=CC=2)=CC=1.[H-].[Na+].[C:45]([O:49][C:50](N1CCC[C@H]1COS(C1C=CC(C)=CC=1)(=O)=O)=[O:51])([CH3:48])([CH3:47])[CH3:46]>CN(C=O)C>[C:50]([N:15]1[CH2:16][CH2:17][CH2:18][C@H:14]1[CH2:13][O:12][C:11]1[CH:19]=[CH:20][C:8]([O:7][C:6]2[CH:21]=[CH:22][C:3]([C:2]([F:1])([F:23])[F:24])=[CH:4][CH:5]=2)=[CH:9][CH:10]=1)([O:49][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:51]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 170230p-(4-(Trifluoromethyl)phenoxy)phenolHCID 11783214tert-Butyl (2S)-2-(((4-methylbenzene-1-sulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 59752995(S)-2-[4-(4-trifluoromethyl-phenoxy)-phenoxymethyl]-pyrrolidine

Product 1

HCID 69002078(S)-N-Boc-2-[4-(4-trifluoromethyl-phenoxy)-phenoxymethyl]-pyrrolidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-2-[4-(4-trifluoromethyl-phenoxy)-phenoxymethyl]-pyrrolidine To a solution of 4-(4-trifluoromethyl-phenoxy)-phenol (1.25 g, 5.0 mmol) in DMF (13 mL) was added 60% NaH (5.0 mmol) at 0° C. and the resulting mixture was stirred at rt for one hour. This was followed by addition of (S)-2-(toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.78 g, 5.0 mmol) in one portion to above reaction and the reaction was heated at 60° C. for 16 h. The mixture was partitioned between water and diethyl ether. The organic layer was washed with brine, dried over anhy. Na2SO4, and concentrated in vacuo to obtain an oil as (S)—N-Boc-2-[4-(4-trifluoromethyl-phenoxy)-phenoxymethyl]-pyrrolidine, which was dissolved in 20 ml of DCM and treated with trifluoroacetic acid (5 mL) at rt for one hour. The reaction was evaporated in vacuo to give a tan oil. Water was added and pH was adjusted to 10 with aqueous saturated Na2CO3 solution. The aqueous phase was extracted with EtOAc and the organic layer was washed with brine, dried over anhy. Na2SO4, and concentrated in vacuo to obtain an oil, which was purified by flash chromatography eluting with 2-5% hexane/EtOAc to afford the title compound (1.45 g, 86%) as a light tan solid: MS; m/z 338 (M+1).

Workup

  1. temperaturethe reaction was heated at 60° C. for 16 h
  2. customThe mixture was partitioned between water and diethyl ether
  3. washThe organic layer was washed with brine
  4. customdried over anhy
  5. concentrationNa2SO4, and concentrated in vacuo

Sources & evidence

ORD record
ord-2108d46f1d5c4f86b90e17bad3fbc8bc
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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