(4R)-3-[(tert-butoxy)carbonyl]-1,3-thiazolidine-4-carboxylic acid → (S)-2-((tert-butoxycarbonyl)amino)-6-((R)-3-(tert-butoxycarbonyl)thiazolidine-4-carboxamido)hexanoic acid

HRID 1482364Notes

Reaction equation

HRID 1482364 reaction equation
[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[C:19]([O:23][C:24]([N:26]1[C@H:30]([C:31]([OH:33])=O)[CH2:29][S:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].[NH2:34][CH2:35][CH2:36][CH2:37][CH2:38][C@H:39]([NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:40]([OH:42])=[O:41]>CN(C=O)C.O>[C:47]([O:46][C:44]([NH:43][C@@H:39]([CH2:38][CH2:37][CH2:36][CH2:35][NH:34][C:31]([C@@H:30]1[CH2:29][S:28][CH2:27][N:26]1[C:24]([O:23][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:25])=[O:33])[C:40]([OH:42])=[O:41])=[O:45])([CH3:50])([CH3:49])[CH3:48]

Participants

6

Reactant 3

HCID 688405(4R)-3-[(tert-butoxy)carbonyl]-1,3-thiazolidine-4-carboxylic acidHCID 2733284epsilon-tert-Butyloxycarbonyl-lysineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride

Product 1

HCID 89668375(S)-2-((tert-butoxycarbonyl)amino)-6-((R)-3-(tert-butoxycarbonyl)thiazolidine-4-carboxamido)hexanoic acidYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (247 mg, 0.892 mmol) was added to a solution of (R)-3-(tert-butoxycarbonyl)thiazolidine-4-carboxylic acid (Compound tk81) (208 mg, 0.892 mmol) in DMF (1 ml), and the mixture was stirred at room temperature for 30 minutes. A solution of (S)-6-amino-2-((tert-butoxycarbonyl)amino)hexanoic acid (220 mg, 0.892 mmol) in water (1 ml) was added dropwise at room temperature over 3 minutes. After completion of the dropwise addition, the mixture was stirred at room temperature for 30 minutes. The reaction solution was purified by reverse-phase silica gel column chromatography (10 mM aqueous ammonium acetate solution/methanol) to afford (S)-2-((tert-butoxycarbonyl)amino)-6-((R)-3-(tert-butoxycarbonyl)thiazolidine-4-carboxamido)hexanoic acid (Compound tk82) (156 mg, 38%).

Workup

  1. additionAfter completion of the dropwise addition
  2. stirringthe mixture was stirred at room temperature for 30 minutes
  3. customThe reaction solution was purified by reverse-phase silica gel column chromatography (10 mM aqueous ammonium acetate solution/methanol)

Sources & evidence

ORD record
ord-e603876dbc2144e586b0b46a2da141cb
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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