Bromoacetonitrile → (S)-tert-butyl 5-((S)-3-((tert-butoxycarbonyl)amino)-4-(cyanomethoxy)-4-oxobutyl)thiazolidine-3-carboxylate

HRID 1482317Notes

Reaction equation

HRID 1482317 reaction equation
[CH:1]([N:4](CC)C(C)C)(C)[CH3:2].BrCC#N.[C:14]([O:18][C:19]([NH:21][C@@H:22]([CH2:26][CH2:27][C@@H:28]1[S:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29]1)[C:23]([OH:25])=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15]>C(#N)C>[C:14]([O:18][C:19]([NH:21][C@H:22]([C:23]([O:25][CH2:2][C:1]#[N:4])=[O:24])[CH2:26][CH2:27][C@@H:28]1[S:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 81531DiisopropylethylamineHCID 89668380(S)-2-((tert-butoxycarbonyl)amino)-4-((S)-3-(tert-butoxycarbonyl) thiazolidin-5-yl)butanoic acid

Product 1

HCID 89668482(S)-tert-butyl 5-((S)-3-((tert-butoxycarbonyl)amino)-4-(cyanomethoxy)-4-oxobutyl)thiazolidine-3-carboxylateYield 87.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N,N-Diisopropylethylamine (48 μL, 0.276 mmol) and subsequently bromoacetonitrile (88 μL, 1.255 mmol) were added to a solution of (S)-2-((tert-butoxycarbonyl)amino)-4-((S)-3-(tert-butoxycarbonyl) thiazolidin-5-yl)butanoic acid (Compound tk2) (98 mg, 0.251 mmol) in acetonitrile (0.5 mL) at room temperature under a nitrogen atmosphere. The reaction mixture was stirred at the same temperature for 3 hours and then concentrated under reduced pressure, and the resulting crude product was purified by normal-phase silica gel column chromatography (hexane/ethyl acetate) to afford (S)-tert-butyl 5-((S)-3-((tert-butoxycarbonyl)amino)-4-(cyanomethoxy)-4-oxobutyl)thiazolidine-3-carboxylate (Compound tk3) (94.0 mg, 87%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customthe resulting crude product was purified by normal-phase silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-9d5fcd91645744f996e6d6abea73554d
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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