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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
Notes
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Reaction equation

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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 2733832Lithium hexamethyldisilazaneHCID 69600916(6S,8RS)-allyl-(8-methyl-4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic Acid Benzyl Ester

Product 1

HCID 69600880(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 esterYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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

  1. temperatureto warm to −40° C. over 20 min
  2. customquenched with NH4Cl
  3. additionThe reaction mixture was diluted with EtOAc
  4. washwashed with H2O, brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. 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

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes