Sodium hydride → (S)-tert-butyl 2-(2-(tert-butoxycarbonylamino)butoxy)acetate

HRID 2204986Notes

Reaction equation

[OH:1][CH2:2][C@@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:4][CH3:5].[H-].[Na+].Br[CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1COCC1>[C:9]([O:8][C:7]([NH:6][C@@H:3]([CH2:4][CH3:5])[CH2:2][O:1][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:13])([CH3:12])([CH3:11])[CH3:10]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (S)-tert-butyl 1-hydroxybutan-2-ylcarbamate (1 eq, from the previous step) in THF (0.23 M) at 0° C. was added portionwise 60% wt NaH (2 eq). The reaction was stirred at 0° C. for 30 minutes, and then a solution of tert-butyl 2-bromoacetate (1 eq) in THF (0.12 M) was added dropwise. The reaction was warmed to room temperature and stirred for 1 hour. The reaction was quenched slowly with saturated aqueous NH4Cl solution and diluted with ether. The organic layer was washed with water, brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using a gradient of 0-40% ethyl acetate in hexanes to give the product as an oil.

Workup

temperatureThe reaction was warmed to room temperature
stirringstirred for 1 hour
customThe reaction was quenched slowly with saturated aqueous NH4Cl solution
additiondiluted with ether
washThe organic layer was washed with water, brine
dry with materialdried over anhydrous MgSO4
concentrationconcentrated en vaccuo
customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record: ord-05e68fc0d85a4d13aa9b1024a6e93039
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365506B2

Reaction notes

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