Trifluoroacetic acid → HCID 67278023, compound

HRID 222899Notes

Reaction equation

HRID 222899 reaction equation
CC(O[C:6]([NH:8][C@@H:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[N:27]=[C:28]3[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][N:29]3[CH:35]=2)=[CH:22][CH:21]=1)[CH2:10][CH2:11][C:12]([O:14]C(C)(C)C)=[O:13])=[O:7])(C)C.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C(NC(C)C)(C)C.[Cl:57][C:58]1[CH:59]=[C:60]([CH:75]=[CH:76][C:77]=1[O:78][CH:79]([CH3:81])[CH3:80])C(OC1C(F)=C(F)C(F)=C(F)C=1F)=O>C(Cl)Cl>[Cl:57][C:58]1[CH:59]=[C:60]([C:6]([NH:8][C@@H:9]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]3[N:27]=[C:28]4[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][N:29]4[CH:35]=3)=[CH:24][CH:25]=2)[CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[O:7])[CH:75]=[CH:76][C:77]=1[O:78][CH:79]([CH3:81])[CH3:80]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7912DiisopropylamineHCID 12052TriethylsilaneHCID 57594128HCID 57594128, compoundHCID 672783711,1-dimethylethyl (4R)-4-(([(1,1-dimethylethyl)oxy]carbonyl}amino)-5-[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]pentanoate

Product 1

HCID 67278023HCID 67278023, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl (4R)-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]pentanoate (1.35 g, 2.82 mmol) in CH2Cl2 (14 mL) was added trifluoroacetic acid (10 mL) followed by triethylsilane (2.5 equiv, 7.04 mmol). The reaction was stirred for 45 minutes at room temperature and then concentrated in vacuo. DMF (35 mL) was added to the residue followed by diisopropylamine (14.7 mL, 84.51 mmol) under nitrogen. The reaction was stirred for 5 minutes and pentafluorophenyl 3-chloro-4-[(1-methylethyl)oxy]benzoate (1.1 equiv, 3.10 mmol) was added. The reaction was stirred for 45 minutes and then concentrated in vacuo. Ethyl acetate (50 mL) was added to the residue and it was washed with H2O (30 mL). The aqueous layer was extracted with EtOAc (20 mL) and the combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification by silica gel chromatography (Analogix IF280, 25-100% EtOAc/hexanes) provided the title compound as a white foamy solid (61%). ESMS [M+H]+=520.2.

Workup

  1. concentrationconcentrated in vacuo
  2. additionDMF (35 mL) was added to the residue
  3. stirringThe reaction was stirred for 5 minutes
  4. stirringThe reaction was stirred for 45 minutes
  5. concentrationconcentrated in vacuo
  6. additionEthyl acetate (50 mL) was added to the residue and it
  7. washwas washed with H2O (30 mL)
  8. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  9. dry with materialthe combined organic layers were dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customPurification by silica gel chromatography (Analogix IF280, 25-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7e807170cde04933ae8f59d122463c9f
Source dataset
uspto-grants-2012_06
Patent number
US08207340B2

Reaction notes

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