Ammonia → (S)-tert-Butyl 2-((1R,2R)-2-(4-bromophenyl)-1-carbamoyl-cyclopropylcarbamoyl)piperidine-1-carboxylate

HRID 600313Notes

Reaction equation

HRID 600313 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:10][C@:9]2([NH:14][C:15]([C@@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][N:18]2[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:16])[C:11]([OH:13])=O)=[CH:4][CH:3]=1.C([N:32]1CCOCC1)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.N>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:10][C@:9]2([NH:14][C:15]([C@@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][N:18]2[C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])=[O:16])[C:11](=[O:13])[NH2:32])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 222Ammonia2×HCID 7525EthylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 57999663(1R,2R)-2-(4-Bromophenyl)-1-((S)-1-(tert-butoxycarbonyl)piperidine-2-carboxamido)cyclopropanecarboxylic Acid

Product 1

HCID 57999645(S)-tert-Butyl 2-((1R,2R)-2-(4-bromophenyl)-1-carbamoyl-cyclopropylcarbamoyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1R,2R)-2-(4-Bromophenyl)-1-((S)-1-(tert-butoxycarbonyl)piperidine-2-carboxamido)cyclopropanecarboxylic acid (3 g) was dissolved in DMF (17 mL) and to the solution was added N-ethylmorpholine (1.219 mL) followed by TBTU (3.09 g). The reaction mixture was stirred at RT for 20 min then it was cooled to 0° C. Aqueous ammonia (1.461 mL) was added and the mixture was allowed to reach RT over 1 h. The reaction appeared to have proceeded ˜70%, so it 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 reextracted into ethyl acetate twice more. The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound (2.75 g) as a pale gum.

Workup

  1. temperatureit was cooled to 0° C
  2. waitto reach RT over 1 h
  3. waitso it 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. dry with materialThe combined organic phases were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d9cc49c1049a4d689ca04d0fae8d1423
Source dataset
uspto-grants-2011_03
Patent number
US07902181B2

Reaction notes

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