Sodium triacetoxyborohydride → benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethylamino]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylate

HRID 708482Notes

Reaction equation

HRID 708482 reaction equation
[NH2:1][CH2:2][C@@H:3]1[C@H:6]([NH:7][C:8](=[O:44])/[C:9](=[N:23]\[O:24][C:25]2([C:28]([O:30][CH:31]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])[CH2:27][CH2:26]2)/[C:10]2[N:11]=[C:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[S:13][CH:14]=2)[C:5](=[O:45])[NH:4]1.O=[CH:47][CH2:48][NH:49][C:50](=[O:66])[O:51][CH2:52][CH:53]1[C:65]2[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=2[C:59]2[C:54]1=[CH:55][CH:56]=[CH:57][CH:58]=2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:55]1[C:54]2[CH:53]([CH2:52][O:51][C:50]([NH:49][CH2:48][CH2:47][NH:1][CH2:2][C@@H:3]3[C@H:6]([NH:7][C:8](=[O:44])/[C:9](=[N:23]\[O:24][C:25]4([C:28]([O:30][CH:31]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)=[O:29])[CH2:27][CH2:26]4)/[C:10]4[N:11]=[C:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[S:13][CH:14]=4)[C:5](=[O:45])[NH:4]3)=[O:66])[C:65]3[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=3)[C:59]=2[CH:58]=[CH:57][CH:56]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 10858926(9H-Fluoren-9-yl)methyl 2-oxoethylcarbamateHCID 118380072benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-(aminomethyl)-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylate

Product 1

HCID 118379524benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethylamino]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylateYield 58%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of benzhydryl 1-(((Z)-(2-(((2R,3S)-2-(aminomethyl)-4-oxoazetidin-3-yl)amino)-1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-oxoethylidene)amino)oxy)cyclopropanecarboxylate (199 mg, 0.29 mmol) in DCE (2.9 mL) was added (9H-fluoren-9-yl)methyl (2-oxoethyl)carbamate (84 mg, 0.30 mmol) and sodium triacetoxyborohydride (181 mg, 0.86 mmol). After 12 h, the reaction mixture was quenched with saturated NaHCO3 (aq), diluted with EtOAc, and the layers were separated. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (MeOH-DCM, 0-100%) to afford the title compound (150 mg, 58%). LCMS: Rt=1.10 min, m/z=900.0 (M+1), Method 2m_acidic. 1H NMR (400 MHz, DMSO-d6): 9.16 (d, J=9.0 Hz, 1H), 8.35 (s, 1H), 7.87 (d, J=7.4 Hz, 2H), 7.66 (d, J=7.4 Hz, 2H), 7.45-7.18 (m, 16H), 6.83 (s, 1H), 5.24-5.17 (m, 1H), 4.28 (d, J=6.7 Hz, 2H), 4.19 (d, J=6.3 Hz, 1H), 3.79-3.67 (m, 1H), 3.03-2.95 (m, 2H), 2.73-2.63 (m, 1H), 1.54-1.37 (m, 13H).

Workup

  1. customthe reaction mixture was quenched with saturated NaHCO3 (aq)
  2. additiondiluted with EtOAc
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified via silica gel chromatography (MeOH-DCM, 0-100%)

Sources & evidence

ORD record
ord-a92d72d83386452fa970d6047c7f93b0
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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