Methyl 4-(bromomethyl)benzoate → Methyl 4-{3-tert-butoxy-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}benzoate

HRID 1919898Notes

Reaction equation

[C:1]([O:5][C:6](=[O:16])[CH2:7][NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([CH3:4])([CH3:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=1>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:16])[CH:7]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

Tert-butyl[(tert-butoxycarbonyl)amino]acetate (1.01 g, 4.37 mmol) was dissolved in THF (10 mL) and cooled to −78° C. LiHMDS (6.5 mL, 1M solution in THF) was slowly added and allowed to stir for 30 minutes. Methyl 4-(bromomethyl)benzoate (1.98 g, 8.64 mmol) in THF (6 mL) was added to the mixture and allowed to stir overnight, slowly warming to room temperature. The reaction was diluted with ethyl acetate and quenched with saturated ammonium chloride. The aqueous layer was extracted three times with ethyl acetate. The combined organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by column chromatography. MS: cal'd 379 (MH+), exp 402 (MH+).

Workup

stirringto stir overnight
temperatureslowly warming to room temperature
customquenched with saturated ammonium chloride
extractionThe aqueous layer was extracted three times with ethyl acetate
dry with materialThe combined organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record: ord-fd8c5cc610c84a5b9d787fb783e8e6d1
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168658B2

Reaction notes

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