Acetone → HCID 86705145, compound

HRID 516453Notes

Reaction equation

HRID 516453 reaction equation
[C:1]([O:4][CH2:5]Br)(=[O:3])[CH3:2].CCOCC.C([O:19][N:20]1[C:24]2[CH:25]=[C:26]([C:29]([NH:31][C@H:32]([CH2:39][C:40]3[CH:45]=[CH:44][C:43]([C:46]4[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=4)=[CH:42][CH:41]=3)[CH2:33][C@@H:34]([OH:38])[C:35]([OH:37])=[O:36])=[O:30])[CH:27]=[CH:28][C:23]=2[N:22]=[N:21]1)C1C=CC=CC=1.CC(C)=O.C1COCC1>[Pd].CC(O)=O>[C:1]([O:4][CH2:5][O:37][C:35](=[O:36])[C@H:34]([OH:38])[CH2:33][C@H:32]([NH:31][C:29]([C:26]1[CH:27]=[CH:28][C:23]2[N:22]=[N:21][N:20]([OH:19])[C:24]=2[CH:25]=1)=[O:30])[CH2:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=2)=[CH:42][CH:41]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 5

HCID 180AcetoneHCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 68536Bromomethyl acetateHCID 72700307HCID 72700307, compound

Product 1

HCID 86705145HCID 86705145, compoundYield 34.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 23938PalladiumSolvent

Conditions

Temperature
45 °C

Procedure

Bromomethyl acetate (6.7 μL, 68.3 μmol) and Et2O (11.7 μL, 84 μmol) were added to a solution of (2R,4R)-4-[(3-benzyloxy-3H-benzotriazole-5-carbonyl)amino]-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid (30.0 mg, 52.5 μmol) in acetone (1.0 mL, 13.6 mmol) and the resulting mixture was stirred at 45° C. for 1 hour. A drop of AcOH was added to neutralize the reaction and the mixture was concentrated to yield a clear yellow liquid. The crude liquid was purified (C18 column chromatography, 55 g column, using 40-90% MeCN in water with 0.05% TFA) to yield a white solid. The solid was dissolved in THF (1.0 mL, 12.3 mmol) and 10% Pd/C, 50% wet (0.45 mmol/g loading; 5.8 mg, 2.6 μmol) was added to the solution, which was stirred under hydrogen for 1 hour. The mixture was filtered and the filtrate was concentrated to yield a clear colorless liquid. The crude liquid was purified (preparative scale C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA) to yield the title compound as a white solid (10.0 mg, purity 99%). MS m/z [M+H]+ calc'd for C27H25ClN4O7, 553.14. found 553.1.

Workup

  1. customthe reaction
  2. concentrationthe mixture was concentrated
  3. customto yield a clear yellow liquid
  4. customThe crude liquid was purified (C18 column chromatography, 55 g column, using 40-90% MeCN in water with 0.05% TFA)
  5. customto yield a white solid
  6. stirringwas stirred under hydrogen for 1 hour
  7. filtrationThe mixture was filtered
  8. concentrationthe filtrate was concentrated
  9. customto yield a clear colorless liquid
  10. customThe crude liquid was purified (preparative scale C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-47feac073fb64191ba5bcd1b0a52e894
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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