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

HRID 1468710Notes

Reaction equation

HRID 1468710 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+].BrBr>CC(O)=O.C1COCC1>[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

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 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 pivalate

Reagents, catalysts & solvents 1

HCID 23444217Acetic acid tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of S)-2-(2-bromo-6-methyl-4-nitrophenyl)-2-tert-butoxyethyl pivalate (9 g, 21.63 mmol) in EtOH (50 ml) and EtOAc (50 ml) was added Pt/C (1.5 g), attached with a balloon of H2. More Pt/C (500 mg) was added after 3 h. Then the reaction mixture was stirred at rt for another 2 h. The reaction mixture was filtered over celite, concentrated down to give product (S)-2-(4-amino-2-bromo-6-methylphenyl)-2-tert-butoxyethyl pivalate (65G) and went to next step without purification. To a solution of (S)-2-(4-amino-2-bromo-6-methylphenyl)-2-tert-butoxyethyl pivalate (65G) (21.63 mmol) in HOAc/THF (80 ml, 1:1) was added KSCN at 0° C. The reaction mixture was stirred at 0° C. for 0.5 h. Then Br2 was added slowly, reacted at 0° C. The reaction was quenched by adding sat. NaHSO3, extracted by EtOAc, dried over MgSO4, purified by silica gel column, eluting by 0-40% EtOAc in Hexanes to give 65H (2.3 g, 24% over 2 steps).

Workup

  1. customwent to next step without purification
  2. customreacted at 0° C
  3. customThe reaction was quenched
  4. additionby adding sat. NaHSO3
  5. extractionextracted by EtOAc
  6. dry with materialdried over MgSO4
  7. custompurified by silica gel column
  8. washeluting by 0-40% EtOAc in Hexanes
  9. customto give 65H (2.3 g, 24% over 2 steps)

Sources & evidence

ORD record
ord-61ed876adb404635a8814fa6dac5517c
Source dataset
uspto-grants-2015_04
Patent number
US09006229B2

Reaction notes

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