(alphaZ)-2-Amino-alpha-((2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy)imino)-4-thiazoleacetic acid → 2-(((1-(tert-Butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid

HRID 525916Notes

Reaction equation

HRID 525916 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:11]/[O:12][C:13]([CH3:22])([CH3:21])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])/[C:8]([OH:10])=[O:9])[N:6]=1>ClCCl.CN(C1C=CN=CC=1)C>[C:17]([O:16][C:14](=[O:15])[C:13]([O:12]/[N:11]=[C:7](/[C:5]1[N:6]=[C:2]([NH:1][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[S:3][CH:4]=1)\[C:8]([OH:10])=[O:9])([CH3:22])[CH3:21])([CH3:20])([CH3:19])[CH3:18]

Participants

4

Reactant 1

HCID 6242497(alphaZ)-2-Amino-alpha-((2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy)imino)-4-thiazoleacetic acid

Product 1

HCID 189632922-(((1-(tert-Butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acidYield 79.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (Z)-2-(2-aminothiazol-4-yl)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)acetic acid (120 g, 364 mmol) in Dichloromethane (DCM) (840 mL) in an ice bath was added TEA (76 mL, 546 mmol), a solution of Boc-anhydride (110 mL, 474 mmol), and DMAP (8.90 g, 72.9 mmol). The mixture was stirred at r.t. over night. The solvent was then removed under vacuum. Water (1 L) and diisopropylether (700 mL) were added to the mixture. The aqueous layer was separated, washed with toluene and was adjusted to pH ˜2 with 2N HCl. The aqueous layer was extracted with toluene. The organic layer was concentrated. IPE was added and the insoluble material was tritulated. The material was collected by filtration and dried to afford (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (69 g, 145 mmol, 39.7% yield) as a white powder. LCMS: (M+H)+: 430.0

Workup

  1. customThe solvent was then removed under vacuum
  2. additionWater (1 L) and diisopropylether (700 mL) were added to the mixture
  3. customThe aqueous layer was separated
  4. washwashed with toluene
  5. extractionThe aqueous layer was extracted with toluene
  6. concentrationThe organic layer was concentrated
  7. additionIPE was added
  8. filtrationThe material was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-906eb39b71f140e7be17d40d736d9657
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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