tert-Butyl bromoacetate → HCID 57500346, compound

HRID 2273528Notes

Reaction equation

HRID 2273528 reaction equation
Br[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[NH2:10][C:11]1[CH:20]=[CH:19][C:18]([C:21]([C:23]2[N:31]3[C:26]([C:27]([OH:32])=[CH:28][CH:29]=[CH:30]3)=[C:25]([O:33][CH3:34])[C:24]=2[CH3:35])=[O:22])=[CH:17][C:12]=1[C:13]([O:15][CH3:16])=[O:14].S([O-])(O)(=O)=O.[K+]>O1CCCC1>[NH2:10][C:11]1[CH:20]=[CH:19][C:18]([C:21]([C:23]2[N:31]3[C:26]([C:27]([O:32][CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])=[CH:28][CH:29]=[CH:30]3)=[C:25]([O:33][CH3:34])[C:24]=2[CH3:35])=[O:22])=[CH:17][C:12]=1[C:13]([O:15][CH3:16])=[O:14]

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 516920Potassium bisulfateHCID 57500344HCID 57500344, compound

Product 1

HCID 57500346HCID 57500346, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5.4 ml (9.31 mmol) of potassium hexamethyldisilylamide (0.5 M solution in toluene) and then 0.69 ml (4.66 mmol) of tert-butyl 2-bromoacetate are added, dropwise, to the solution of 1.50 g (4.23 mmol) of methyl 2-amino-5-[(8-hydroxy-1-methoxy-2-methylindolizin-3-yl)carbonyl]benzoate (Stage F of Example 1) in 15 ml of tetrahydrofuran at −20° C. under argon. The mixture is stirred for 2 hours, allowing it to return to ambient temperature. The reaction medium is poured into a saturated aqueous solution of potassium hydrogen sulphate and the mixture is extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, and concentrated under reduced pressure. The oil obtained is purified by flash chromatography on silica gel (dichloromethane/methanol gradient=100/0 to 90/10). 1.26 g (64%) of a yellow powder are obtained.

Workup

  1. customat −20° C.
  2. customto return to ambient temperature
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe organic phase is washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe oil obtained
  8. customis purified by flash chromatography on silica gel (dichloromethane/methanol gradient=100/0 to 90/10)

Sources & evidence

ORD record
ord-ea8ae72328784260bbef0bebaf304fa7
Source dataset
uspto-grants-2015_09
Patent number
US09120819B2

Reaction notes

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