Trifluoroacetic acid → HCID 118379301, compound

HRID 708396Notes

Reaction equation

HRID 708396 reaction equation
C([O:14][C:15]([C:17]1([O:20]/[N:21]=[C:22](/[C:50]2[N:51]=[C:52]([NH:55]C(OC(C)(C)C)=O)[S:53][CH:54]=2)\[C:23]([NH:25][C@@H:26]2[C:29](=[O:30])[N:28]([S:31]([OH:34])(=[O:33])=[O:32])[C@@H:27]2[CH2:35][N:36]2[CH:40]=[C:39]([CH2:41][NH:42]C(OC(C)(C)C)=O)[N:38]=[N:37]2)=[O:24])[CH2:19][CH2:18]1)=[O:16])(C1C=CC=CC=1)C1C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:42][CH2:41][C:39]1[N:38]=[N:37][N:36]([CH2:35][C@@H:27]2[C@H:26]([NH:25][C:23](=[O:24])/[C:22](=[N:21]\[O:20][C:17]3([C:15]([OH:16])=[O:14])[CH2:19][CH2:18]3)/[C:50]3[N:51]=[C:52]([NH2:55])[S:53][CH:54]=3)[C:29](=[O:30])[N:28]2[S:31]([OH:34])(=[O:33])=[O:32])[CH:40]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid3×HCID 118379558HCID 118379558, compound

Product 1

HCID 118379301HCID 118379301, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Followed the general procedure for the acid mediated deprotection using (2R,3S)-3-((Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-2-((4-(((tert-butoxycarbonyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)-4-oxoazetidine-1-sulfonic acid (1.74 g, 1.94 mmol), DCM (19.4 mL) and TFA (8.95 mL, 116 mmol). After 3 h at rt, it was cooled to 0° C. and more TFA (200 μL, 2.6 mmol) was added whereupon it was allowed to warm to rt. After another 1 h at rt, it was cooled to 0° C. and more TFA (200 μL, 2.6 mmol) was added, again allowing to warm to rt. After an additional 1 h at rt it was diluted with DCM and concentrated in vacuo. Half of the crude residue was purified by reverse phase prep HPLC (XSelect CSH, 30×100 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 60 mL/min), affording the title compound (140 mg, ca 23%) as a white powder. LCMS: Rt=0.27 min, m/z=530.1 (M+1) Method 2m_acidic; 1H NMR (400 MHz, D2O) δ 8.07 (s, 1H), 7.08-6.99 (m, 1H) 5.42-5.31 (m, 1H), 4.88-4.74 (m, 2H assumed; partially obscured by solvent residual peak), 4.74-4.68 (m, 1H), 4.20 (s, 2H), 1.36-1.23 (m, 2H), 1.23-1.07 (m, 2H).

Workup

  1. temperatureto warm to rt
  2. waitAfter another 1 h at rt
  3. temperatureit was cooled to 0° C.
  4. temperatureto warm to rt
  5. concentrationconcentrated in vacuo
  6. customHalf of the crude residue was purified by reverse phase prep HPLC (XSelect CSH, 30×100 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 60 mL/min)

Sources & evidence

ORD record
ord-20c1e5b65f804d9294298edfba22ba4f
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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