Ammonia → (S)-tert-butyl 1-amino-1-oxo-3-(4-(phenylsulfonyl)phenyl)propan-2-ylcarbamate

HRID 600338Notes

Reaction equation

HRID 600338 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:31]1CCOCC1)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.N>CN(C=O)C>[NH2:31][C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)(=[O:21])=[O:22])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 222Ammonia2×HCID 7525EthylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 57999674(S)-2-(tert-Butoxycarbonylamino)-3-(4-(phenylsulfonyl)phenyl)propanoic Acid

Product 1

HCID 57999655(S)-tert-butyl 1-amino-1-oxo-3-(4-(phenylsulfonyl)phenyl)propan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-2-(tert-Butoxycarbonylamino)-3-(4-(phenylsulfonyl)phenyl)propanoic acid (675 mg) was dissolved in DMF (8 mL) and to the solution was added N-ethylmorpholine (0.316 mL) followed by TBTU (802 mg). The reaction mixture was stirred at room temperature for 20 min then it was cooled to 0° C. Aqueous ammonia (0.379 mL) was added and the mixture was allowed to reach room temperature over 1 h. The reaction mixture was left to stir for a further 2 h. LCMS showed little change so further TBTU (400 mg) and ammonia (0.3 mL) were added, and the mixture stirred for a further 2 h. The reaction mixture was partitioned between ethyl acetate and diluted brine, and the aqueous phase was extracted into ethyl acetate twice more. The combined organic phases were dried over sodium sulphate, filtered and concentrated in vacuo to yield a pale gum. This was purified by flash silica chromatography, eluting with ethyl acetate to give the subtitle compound (450 mg) as a colourless gum.

Workup

  1. temperatureit was cooled to 0° C
  2. waitto reach room temperature over 1 h
  3. waitThe reaction mixture was left
  4. stirringto stir for a further 2 h
  5. additionwere added
  6. stirringthe mixture stirred for a further 2 h
  7. customThe reaction mixture was partitioned between ethyl acetate and diluted brine
  8. extractionthe aqueous phase was extracted into ethyl acetate twice more
  9. dry with materialThe combined organic phases were dried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto yield a pale gum
  13. customThis was purified by flash silica chromatography
  14. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-a4b566fb030a4975b4b7a3e598df6dd3
Source dataset
uspto-grants-2011_03
Patent number
US07902181B2

Reaction notes

Loading…