tert-Butyl bromoacetate → (6R,8S)-[3-(allyl-benzyloxycarbonyl-amino)-8-methyl-4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl]-acetic acid tert-butyl ester

HRID 11001

Reaction equation

[CH2:1]([O:8][C:9](=[O:34])[N:10]([CH2:31][CH:32]=[CH2:33])[C:11]1[C:16](=[O:17])[N:15]2[C@H:18]([C:22](=[O:30])[NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:19][CH:20]([CH3:21])[C:14]2=[N:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:46][C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48]>C1COCC1>[C:50]([O:49][C:47](=[O:48])[CH2:46][C@@:20]1([CH3:21])[C:14]2=[N:13][CH:12]=[C:11]([N:10]([CH2:31][CH:32]=[CH2:33])[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:34])[C:16](=[O:17])[N:15]2[C@@H:18]([C:22](=[O:30])[NH:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:19]1)([CH3:53])([CH3:52])[CH3:51]

Participants

Conditions

Temperature: -78 °C

Procedure

To Intermediate 18c (495.7 mg, 1.08 mmol) in THF at −78° C. was added LiHMDS (2.268 mL, 2.268 mmol) dropwise. After 10 min, tert-butyl bromoacetate was added and the mixture was stirred at −78° C. for 20 min. It was allowed to warm to −40° C. over 20 min, then quenched with NH4Cl. The reaction mixture was diluted with EtOAc, then washed with H2O, brine, dried (Na2SO4) and concentrated. It was purified by SiO2 chromatography (50% EtOAc/hexanes) to afford 367.9 mg (59%) of intermediate 38a.

Workup

temperatureto warm to −40° C. over 20 min
customquenched with NH4Cl
additionThe reaction mixture was diluted with EtOAc
washwashed with H2O, brine
dry with materialdried (Na2SO4)
concentrationconcentrated
customIt was purified by SiO2 chromatography (50% EtOAc/hexanes)

Sources & evidence

ORD record: ord-d64943344df842839afee007706c4b16
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07094783B2

Linked notes

Loading…