Cesium carbonate → [(S)-1-(2-{[4-(4-Trifluoromethoxybenzyloxy)phenyl]-[(E)-(3-phenylacryloyl)]-amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

HRID 468613Notes

Reaction equation

HRID 468613 reaction equation
[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8]Br)=[CH:6][CH:5]=1.[OH:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]([C:38](=[O:47])/[CH:39]=[CH:40]/[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:22][C:23]([N:25]2[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]2)=[O:24])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8][O:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]([C:38](=[O:47])/[CH:39]=[CH:40]/[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH2:22][C:23]([N:25]3[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]3)=[O:24])=[CH:17][CH:16]=2)=[CH:6][CH:5]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 1427851-(Bromomethyl)-4-(trifluoromethoxy)benzeneHCID 59212003[(S)-1-(2-{(4-Hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

Product 1

HCID 86618488[(S)-1-(2-{[4-(4-Trifluoromethoxybenzyloxy)phenyl]-[(E)-(3-phenylacryloyl)]-amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl esterYield 75%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Trifluoromethoxybenzyl bromide (17 μL) was added to a mixture of [(S)-1-(2-{(4-hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]-carbamic acid, tert-butyl ester 14 (50 mg, 0.11 mmol), cesium carbonate (52 mg, 0.16 mmol) and TBAI (40 mg, 0.11 mmol) in DMF (3 mL). The reaction mixture was stirred at room temperature overnight and then diluted with ethyl acetate and washed with 10% hydrochloric acid (×2) and brine, dried (Na2SO4) and evaporated to dryness. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate/petrol (2:1) to afford the title compound as a colourless foam (52 mg, 75%). 1HNMR (300 MHz) (CDCl3) □ 1.41 (9H, s), 1.7-2.2 (2H, m), 3.35-3.8 (4H, m), 4.15-4.35 (2H, m), 4.5 (1H, m), 4.7-4.9 (1H, m), 5.00 (2H, s), 6.37 (1H, d, J=16 Hz), 6.95 (2H, d), 7.18-7.30 (7H, m), 7.32 (2H, d), 7.45 (2H,d) and 7.64 (1H, d, J=16 Hz).

Workup

  1. washwashed with 10% hydrochloric acid (×2) and brine
  2. dry with materialdried (Na2SO4)
  3. customevaporated to dryness
  4. customThe residue was purified by flash column chromatography on silica gel
  5. washeluting with ethyl acetate/petrol (2:1)

Sources & evidence

ORD record
ord-7e2893b99b89478b9b0a692eb6c6d09e
Source dataset
uspto-grants-2014_01
Patent number
US08624022B2

Reaction notes

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