Methanol → (3S)-3-(3-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}phenyl)-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid

HRID 526328Notes

Reaction equation

HRID 526328 reaction equation
[F:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]([C@@H:17]([NH:23][C:24]([C@@H:26]2[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:48])[CH2:33][CH2:34][CH:35]3[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH2:36]3)[CH2:27]2)=[O:25])[CH2:18][C:19]([O:21]C)=[O:20])[CH:14]=[CH:15][CH:16]=1.CO.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>C(O)(C)(C)C>[F:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]([C@@H:17]([NH:23][C:24]([C@@H:26]2[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:48])[CH2:33][CH2:34][CH:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[CH2:27]2)=[O:25])[CH2:18][C:19]([OH:21])=[O:20])[CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 17749109Barium hydroxide, octahydrateHCID 71609267tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(3-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}phenyl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 71609420(3S)-3-(3-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}phenyl)-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acidYield 55%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

Tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(3-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}phenyl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (20.3 mg, 27 μmol) was solved in tert.-butanol (0.77 mL) and methanol (0.76 mL) and barium hydroxide octahydrate (42 mg, 0.13 mmol) was added. After stirring for 60 minutes room temperature the solvent was distilled off at 0° C. by high vacuum. The residue was solved in water (1 mL) and acidified by formic acid (2 mL). After 18 hours at 5° C. additional formic acid (2 mL) was added. After 3 hours at room temperature the solvent was distilled off at 0° C. by high vacuum and the residue was purified by preparative HPLC to yield 8.4 mg of (3S)-3-(3-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}phenyl)-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid.

Workup

  1. distillationwas distilled off at 0° C. by high vacuum
  2. additionAfter 18 hours at 5° C. additional formic acid (2 mL) was added
  3. distillationAfter 3 hours at room temperature the solvent was distilled off at 0° C. by high vacuum
  4. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ba161ce2bcbf411dade199fd0d051d16
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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