Trifluoroacetic acid → HCID 51348416, compound

HRID 1958625Notes

Reaction equation

HRID 1958625 reaction equation
[C:1](=[O:36])([O:5][C:6]([CH3:35])([CH3:34])[CH2:7][NH:8][C:9]([NH:11][C@H:12]([CH:31]([CH3:33])[CH3:32])[C:13]([N:15]1[CH2:20][CH2:19][C@@:18]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)([OH:21])[C:17]([CH3:30])([CH3:29])[CH2:16]1)=[O:14])=[O:10])[O:2][CH2:3]Cl.C(N(CC)CC)C.[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]/[C:47]([OH:49])=[O:48].C(O)(C(F)(F)F)=O>CN(C=O)C.O.CC#N>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([C@@:18]2([OH:21])[CH2:19][CH2:20][N:15]([C:13]([C@H:12]([NH:11][C:9](=[O:10])[NH:8][CH2:7][C:6]([CH3:35])([CH3:34])[O:5][C:1](=[O:36])[O:2][CH2:3][O:51][C:44](=[O:50])/[CH:45]=[CH:46]/[C:47]([OH:49])=[O:48])[CH:31]([CH3:33])[CH3:32])=[O:14])[CH2:16][C:17]2([CH3:29])[CH3:30])=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 8471TriethylamineHCID 444972Fumaric AcidHCID 58215051HCID 58215051, compound

Product 1

HCID 51348416HCID 51348416, compoundYield 20.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
70 °C

Procedure

To chloromethyl 1-(3-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)ureido)-2-methylpropan-2-yl carbonate (0.19 g, 0.348 mmol) in DMF (2 mL) are sequentially added triethylamine (0.048 mL, 0.348 mmol) and fumaric acid (0.020 g, 0.174 mmol) at RT. Contents heated at 70° C. (oil bath temp.) for 20 h. The reaction mixture was cooled to rt and subjected to prep. HPLC (Phenomex Luna AXIA 30×100 mm; 10 min. gradient; solvent A=10% CH3CN, 90% H2O, 0.1% TFA, solvent B=90% CH3CN, 10% H2O, 0.1% TFA). The desired fractions are collected and concentrated. The residue is partitioned between DCM (20 mL) and brine (10 mL). The DCM layer is dried over sodium sulfate and concentrated to yield (R,E)-3-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl)-2,8,8-trimethyl-5,10,14-trioxo-9,11,13-trioxa-4,6-diazaheptadec-15-en-17-oic acid (0.022 g, 0.035 mmol, 10.11% yield).

Workup

  1. customat RT
  2. temperatureThe reaction mixture was cooled to rt
  3. customThe desired fractions are collected
  4. concentrationconcentrated
  5. customThe residue is partitioned between DCM (20 mL) and brine (10 mL)
  6. dry with materialThe DCM layer is dried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-984b0a13d5ed463a86a5dad6a4902765
Source dataset
uspto-grants-2013_04
Patent number
US08410139B2

Reaction notes

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