Diisopropylethylamine → tert-butyl 3-(2-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza bicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-2-oxoethyl)azetidine-1-carboxylate

HRID 1427665Notes

Reaction equation

HRID 1427665 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:34]([O:41][N:42]1[C:48](=[O:49])[N:47]2[CH2:50][C@H:43]1[CH2:44][CH2:45][C@H:46]2[C:51]([OH:53])=O)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[NH:54]([C:56](=[O:69])[CH2:57][CH:58]1[CH2:61][N:60]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:59]1)[NH2:55]>C(Cl)Cl>[CH2:34]([O:41][N:42]1[C:48](=[O:49])[N:47]2[CH2:50][C@H:43]1[CH2:44][CH2:45][C@H:46]2[C:51]([NH:55][NH:54][C:56](=[O:69])[CH2:57][CH:58]1[CH2:61][N:60]([C:62]([O:64][C:65]([CH3:67])([CH3:66])[CH3:68])=[O:63])[CH2:59]1)=[O:53])[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57389355(2S,5R)-6-(Benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acidHCID 67355105Tert-butyl 3-(2-hydrazinyl-2-oxoethyl)azetidine-1-carboxylate

Product 1

HCID 86701039tert-butyl 3-(2-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza bicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-2-oxoethyl)azetidine-1-carboxylateYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

HATU (19.6 g, 52.2 mmol) and DIPEA (16.6 g, 130.5 mmol) were added to a 0° C. solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carboxylic acid (12.0 g, 43.5 mmol), tert-butyl 3-(2-hydrazinyl-2-oxoethyl)azetidine-1-carboxylate (11.3 g, 49.8 mmol) in CH2Cl2 (360 mL). The mixture was allowed to warm to rt then the mixture was stirred at rt for 12 hrs. The mixture was then diluted with CH2Cl2 (300 mL), washed with water (2×) and saturated sodium chloride (2×), dried and concentrated. The residue was purified by silica gel column chromatography (0-20% gradient elution EtOAc/petroleum ether) to afford tert-butyl 3-(2-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza bicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-2-oxoethyl)azetidine-1-carboxylate (19.3 g, 93%) as a white solid. ESI-MS (EI+, m/z): 488 [M+H]+.

Workup

  1. washwashed with water (2×) and saturated sodium chloride (2×)
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel column chromatography (0-20% gradient elution EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-f9064b812cca4eb7a7323f8e4745f1a2
Source dataset
uspto-grants-2015_01
Patent number
US08933233B2

Reaction notes

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