Bromoacetyl bromide → 2-(2-Bromoacetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

2-Amino-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (4.6 g, 19.14 mmol) and DIPEA (4.95 g, 6.33 mL, 38.3 mmol) were dissolved in THF (100 mL) and the mixture purged with nitrogen and cooled in an ice bath. 2-Bromoacetyl bromide (3.86 g, 1.667 mL, 19.14 mmol) dissolved in THF (5 mL) was added dropwise and the reaction monitored by TLC. After 30 min TLC indicated 3:1 product: starting material with a faint spot for bis-acylated material. An additional quantity of 2-bromoacetyl bromide (0.97 g, 0.417 μL, 4.79 mmol) was added and stirring continued for a further 30 min. The mixture was quenched by addition of water before removal of THF under reduced pressure. The mixture was then partitioned between EtOAc/water and the organic layer collected—additional DCM was added to aid solubility. The aqueous layer was further washed with DCM. Combined organics were dried and concentrated to give a thick dark oil which was purified on silica eluting with 20-60% EtOAc/heptane. Desired fractions were collected and concentrated to yield the desired product as a light yellow solid (2.96 g, 8.23 mmol, 43%). The sample was used directly in the next step without any further purification.

1. customthe mixture purged with nitrogen
2. temperaturecooled in an ice bath
3. additionwas added dropwise
4. waitcontinued for a further 30 min
5. customThe mixture was quenched by addition of water before removal of THF under reduced pressure
6. customThe mixture was then partitioned between EtOAc/water
7. additionthe organic layer collected—additional DCM was added to aid solubility
8. washThe aqueous layer was further washed with DCM
9. customCombined organics were dried
10. concentrationconcentrated
11. customto give a thick dark oil which
12. customwas purified on silica eluting with 20-60% EtOAc/heptane
13. customDesired fractions were collected
14. concentrationconcentrated

ORD record

ord-b12546f1c78145ddad1adafdee8649f0

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07820707B2