((3R,6S)-6-(1,2,4-thiadiazol-5-yl)piperidin-3-yl)(benzyloxy)carbamic chloride HCl salt → (2S,5R)-6-(benzyloxy)-2-(1,2,4-thiadiazol-5-yl)-1,6-diazabicyclo[3.2.1]octan-7-one

HRID 870877Notes

Reaction equation

HRID 870877 reaction equation
Cl.[S:2]1[C:6]([C@H:7]2[NH:12][CH2:11][C@H:10]([N:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:14](Cl)=[O:15])[CH2:9][CH2:8]2)=[N:5][CH:4]=[N:3]1>C(Cl)Cl>[CH2:18]([O:17][N:13]1[C:14](=[O:15])[N:12]2[CH2:11][C@H:10]1[CH2:9][CH2:8][C@H:7]2[C:6]1[S:2][N:3]=[CH:4][N:5]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

3

Reactant 1

HCID 89886521((3R,6S)-6-(1,2,4-thiadiazol-5-yl)piperidin-3-yl)(benzyloxy)carbamic chloride HCl salt

Product 1

HCID 86701420(2S,5R)-6-(benzyloxy)-2-(1,2,4-thiadiazol-5-yl)-1,6-diazabicyclo[3.2.1]octan-7-oneYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of ((3R,6S)-6-(1,2,4-thiadiazol-5-yl)piperidin-3-yl)(benzyloxy)carbamic chloride HCl salt in dry DCM (15 mL) at 0° C. was added TEA (606 mg, 6.0 mmol). The mixture was stirred at rt for 2 hrs and then concentrated. The residue was purified by silica gel column chromatography (3:1 petroleum ether/EtOAc) to give (2S,5R)-6-(benzyloxy)-2-(1,2,4-thiadiazol-5-yl)-1,6-diazabicyclo[3.2.1]octan-7-one (190 mg, 51%) as a yellow solid. ESI-MS (EI+, m/z): 317 [M+H]+. 1HNMR (500 M, CDCl3): δ 8.62 (s, 1H), 7.46-7.37 (m, 5H), 5.09 (d, J=11.2 Hz, 1H), 4.92 (d, J=11.2 Hz, 1H), 4.90 (br d, J=5.5 Hz, 1H), 3.35 (m, 1H), 2.88 (br d, J=6.0 Hz, 1H), 2.79 (d, J=12.0 Hz, 1H), 2.31-2.28 (m, 2H), 2.21-2.11 (m, 1H), 1.98-1.90 (m, 1H).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by silica gel column chromatography (3:1 petroleum ether/EtOAc)

Sources & evidence

ORD record
ord-e748fe64bf2641878144c0c68b8e2fb6
Source dataset
uspto-grants-2015_03
Patent number
US08969570B2

Reaction notes

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