Acetic Acid → HCID 54401251, compound

HRID 1368955Notes

Reaction equation

HRID 1368955 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.CON(C)[C:16]([CH:18]([NH:27][C:28]([CH:30]([NH:35][C:36](=[O:45])[O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:31][CH:32]([CH3:34])[CH3:33])=[O:29])[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:17].C(O)(=O)C>C1COCC1.CCCCC.C(OCC)C>[CH3:33][CH:32]([CH3:34])[CH2:31][CH:30]([NH:35][C:36](=[O:45])[O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:28](=[O:29])[NH:27][CH:18]([C:16]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)=[O:17])[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 79732-BromopyridineHCID 54260837HCID 54260837, compoundHCID 178418339Butyllithium

Product 1

HCID 54401251HCID 54401251, compoundYield 26.6%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution comprised of 2-bromopyridine (0.291 mL, 3.06 mmol) in dry THF (2 mL) was cooled to −78° C. and then a solution of n-butyllithium (1.6 mL, 2.72 mmol) in pentane was added dropwise over 2 minutes. The mixture was stirred at −78° C. for 10 minutes and then a solution of benzyl 1-[1-(N-methoxy-N-methylcarbamoyl)-3-phenylpropylcarbamoyl]-3-methylbutylcarbamate (0.3 g, 0.64 mmol) in THF (2 mL) was added slowly. The mixture was stirred, while allowing to slowly warm to room temperature, and then poured into a solution comprising acetic acid (0.163 mL) in diethyl ether (50 mL). The organic phase was washed with brine (40 mL), dried (MgSO4) and concentrated in vacuo. Product was purified from the residue by flash chromatography on silica gel eluting with 1:2 ethyl acetate/hexanes to provide benzyl 3-methyl-1-(1-pyrid-2-ylcarbonyl-3-phenylpropylcarbamoyl)butylcarbamate (82 mg, 0.17 mmol) as a white solid. MS (ESI) m/z=488 (M+1); 1H NMR (CDCl3): δ 0.8-1.05 (d, J=4 Hz, 6H), 1.5 (m, 1H), δ 1.6-1.78 (t, 2H), δ 1.99-2.20 (m, 1H), δ 2.6-2.9 (m, 1H), δ 2.55-2.85 (m, 2H), δ 4.25 (m, 1H), δ 5.17 (s, 2H), δ 5.25 (m, 1H), δ 6.00 (m, 1H), δ 6.85-6.95 (d, J=10 Hz, 1H), δ 7.1-7.4 (m, 10H) 7.50(t, J=4 Hz, 1H), δ 7.85 (t, J=6 Hz, 1H) 8.01 (d, J=8 hz, 1H), δ 8.69 (m, 1H). Anal (C29H33N3O4).

Workup

  1. stirringThe mixture was stirred
  2. temperatureto slowly warm to room temperature
  3. washThe organic phase was washed with brine (40 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customProduct was purified from the residue by flash chromatography on silica gel eluting with 1:2 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-54a62e20b7e348b79e9c80ddbc0f6979
Source dataset
uspto-grants-2003_06
Patent number
US06576630B1

Reaction notes

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