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

HRID 655187Notes

Reaction equation

HRID 655187 reaction equation
C(N=C=NCCCN(C)C)C.[OH:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]([CH2:30][C:31]([OH:33])=O)[C:20](=[O:29])/[CH:21]=[CH:22]/[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:15][CH:14]=1.ON1C2N=CC=CC=2N=N1.[C:44]([O:48][C:49]([NH:51][C@H:52]1[CH2:56][CH2:55][NH:54][CH2:53]1)=[O:50])([CH3:47])([CH3:46])[CH3:45].CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C>[OH:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]([C:20](=[O:29])/[CH:21]=[CH:22]/[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:30][C:31]([N:54]2[CH2:55][CH2:56][C@H:52]([NH:51][C:49](=[O:50])[O:48][C:44]([CH3:46])([CH3:45])[CH3:47])[CH2:53]2)=[O:33])=[CH:17][CH:18]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 59212013{(4-Hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetic acid

Product 1

HCID 59212003[(S)-1-(2-{(4-Hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl esterYield 72.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide (0.36 g, 1.87 mmol) was added to a solution of {(4-hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetic acid 13 (0.37 g, 1.24 mmol), 1-hydroxy-7-azabenzotriazole (0.25 g, 1.87 mmol), (3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine (0.35 g, 1.87 mmol) and N-methyl-morpholine (0.27 mL, 2.5 mmol) in DMF (40 mL). The reaction mixture was stirred at room temperature for 3 days and then diluted with ethyl acetate and washed with 10% hydrochloric acid (×2), brine, NaHCO3 (×2) and brine, dried (Na2SO4) and evaporated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate/petrol (4:1)→ethyl acetate, to give the title compound as a white powder (0.419 g, 72%). 1HNMR (300 MHz) (CDCl3) δ 1.45 (9H, s), 1.8-2.25 (2H, m), 3.4-3.8 (4H, m), 4.15 (1H, m), 4.6 (1H, m), 5.3 (1H, m), 6.43 (1H, d, J=16), 6.87 (2H, d), 7.2-7.32 (7H, m) and 7.65 (1H, d, J=16 Hz).

Workup

  1. washwashed with 10% hydrochloric acid (×2), brine, NaHCO3 (×2) and brine
  2. dry with materialdried (Na2SO4)
  3. customevaporated
  4. customThe residue was purified by column chromatography on silica gel
  5. washeluting with ethyl acetate/petrol (4:1)→ethyl acetate

Sources & evidence

ORD record
ord-b31efcd2787748cf91224b259a79aafe
Source dataset
uspto-grants-2011_12
Patent number
US08071582B2

Reaction notes

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