Potassium thiocyanate → (S)-2-(2-amino-7-bromo-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyethyl pivalate

HRID 510258Notes

Reaction equation

HRID 510258 reaction equation
[C:1]([O:7][CH2:8][C@H:9]([C:15]1[C:20]([CH3:21])=[CH:19][C:18]([NH2:22])=[CH:17][C:16]=1[Br:23])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[C:24]([S-:26])#[N:25].[K+].[NH+]1C=CC=CC=1.C([O-])(O)=O.[Na+]>CC(O)=O>[C:1]([O:7][CH2:8][C@H:9]([C:15]1[C:20]([CH3:21])=[CH:19][C:18]2[N:22]=[C:24]([NH2:25])[S:26][C:17]=2[C:16]=1[Br:23])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])(=[O:6])[C:2]([CH3:3])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 516872Potassium thiocyanateHCID 516892Sodium BicarbonateHCID 4989215PyridiniumHCID 86699788(S)-2-(4-amino-2-bromo-6-methylphenyl)-2-tert-butoxyethyl pivalate

Product 1

HCID 86699789(S)-2-(2-amino-7-bromo-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyethyl pivalateYield 34.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of freshly prepared (S)-2-(4-amino-2-bromo-6-methylphenyl)-2-tert-butoxyethyl pivalate (7 g, 18.1 mmol) in HOAc (90 mL) was added KSCN (1.76 g, 18.1 mmol) at r.t. The reaction mixture was stirred at r.t. for 0.5 h. Pyridinium perbromide (5.79 g, 18.1 mmol) was added slowly over a period of 10 min, and stirred at r.t for 2 h. The mixture was alkalized to pH=8 using saturated aqueous NaHCO3 solution, then extracted with EtOAc (3×600 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated in vacuo, and purified by silica gel column (Petroleum Ether:EtOAc (10:1→5:1)) to afford (S)-2-(2-amino-7-bromo-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyethyl pivalate (2.74 g, 34.3%) as yellow solid. LCMS-ESI+: calc'd for C19H27BrN2O3S: 443.1 and 445.1 (M+H+); found: 443.1 and 445.1 (M+H+). 1H-NMR: 400 MHz, (CD3OD) δ: 7.15 (s, 1H), 5.53-5.49 (m, 1H), 4.31-4.26 (m, 1H), 4.17-4.13 (m, 1H), 2.64 (s, 3H), 1.15 (s, 9H), 1.11 (s, 9H).

Workup

  1. stirringstirred at r.t for 2 h
  2. extractionextracted with EtOAc (3×600 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by silica gel column (Petroleum Ether:EtOAc (10:1→5:1))

Sources & evidence

ORD record
ord-7eb8350a5dcd40669f5e9b9b74330fa9
Source dataset
uspto-grants-2015_08
Patent number
US09096586B2

Reaction notes

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