tert-butyl ((2S,3S)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxo-3-(pent-4-en-1-yloxy)pentan-2-yl)carbamate → tert-butyl ((2R,6S,7S,13aS,14aR,16aS,Z)-7-ethyl-2-hydroxy-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa[i]pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-6-yl)carbamate

HRID 523187Notes

Reaction equation

HRID 523187 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7](=[O:26])[C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C@@H:9]([O:12][CH2:13][CH2:14][CH2:15][CH:16]=[CH2:17])[CH2:10][CH3:11])[C@H:4]([C:27](=[O:44])[NH:28][C@:29]2([C:34](=[O:43])[NH:35][S:36]([C:39]3([CH3:42])[CH2:41][CH2:40]3)(=[O:38])=[O:37])[CH2:31][C@H:30]2C=C)[CH2:3]1>CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.ClCCCl>[CH2:10]([C@H:9]1[C@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:22])[CH3:23])[C:7](=[O:26])[N:5]2[CH2:6][C@H:2]([OH:1])[CH2:3][C@H:4]2[C:27](=[O:44])[NH:28][C@:29]2([C:34](=[O:43])[NH:35][S:36]([C:39]3([CH3:42])[CH2:40][CH2:41]3)(=[O:38])=[O:37])[CH2:31][C@H:30]2[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH3:11]

Participants

4

Reactant 1

HCID 118425561tert-butyl ((2S,3S)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxo-3-(pent-4-en-1-yloxy)pentan-2-yl)carbamate

Product 1

HCID 90121289tert-butyl ((2R,6S,7S,13aS,14aR,16aS,Z)-7-ethyl-2-hydroxy-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa[i]pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-6-yl)carbamate

Reagents, catalysts & solvents 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a round-bottom flask equipped with a stir bar was added tert-butyl ((2S,3S)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxo-3-(pent-4-en-1-yloxy)pentan-2-yl)carbamate (all material from step 4, 480 mg, 0.749 mmol) and DCE (100 mL). The solution was sparged with nitrogen for 30 minutes. To the solution was added Hoveyda-Grubbs Catalyst 2nd Generation (23 mg, 0.037 mmol). The solution was stirred at 80° C. for 2 h, then was cooled to 45° C. and was stirred for 3 days. The solution was concentrated in vacuo and the resulting residue was subjected to C18 chromatography (water with 0.1% TFA:acetonitrile with 0.1% TFA, 60:40 to 0:100) to afford tert-butyl ((2R,6S,7S,13aS,14aR,16aS,Z)-7-ethyl-2-hydroxy-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa[i]pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-6-yl)carbamate as a brown solid foam (100 mg, 22%). MS: MS m/z 613.4 (M++1).

Workup

  1. customTo a round-bottom flask equipped with a stir bar
  2. customThe solution was sparged with nitrogen for 30 minutes
  3. temperaturewas cooled to 45° C.
  4. stirringwas stirred for 3 days
  5. concentrationThe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-ee87e2ee5c6a42d487bb7c6a6fbb37f0
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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