Iodoethane → (s)-Allyl-(8,8-diethyl-4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic acid benzyl ester

HRID 11000

Reaction equation

HRID 11000 reaction equation
[CH2:1]([O:8][C:9](=[O:33])[N:10]([CH2:30][CH:31]=[CH2:32])[C:11]1[C:16](=[O:17])[N:15]2[C@H:18]([C:21](=[O:29])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:19][CH2:20][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.[CH2:44](I)[CH3:45].[CH2:47]1COC[CH2:48]1>>[CH2:1]([O:8][C:9](=[O:33])[N:10]([CH2:30][CH:31]=[CH2:32])[C:11]1[C:16](=[O:17])[N:15]2[C@H:18]([C:21](=[O:29])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:19][C:20]([CH2:44][CH3:45])([CH2:47][CH3:48])[C:14]2=[N:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 6340Iodoethane2×HCID 8028TetrahydrofuranHCID 2733832Lithium Hexamethyldisilazide2×HCID 69600602(6S)-allyl-(4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic Acid Benzyl Ester

Product 1

HCID 69600906(s)-Allyl-(8,8-diethyl-4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic acid benzyl esterYield 72%

Conditions

Temperature
-78 °C

Procedure

To a solution of phenyl amide 18b (100 mg, 0.225 mmol) in 1 mL THF at −78° C., was added LiHMDS (IM in THF, 0.720 mL, 0.720 mmol). The orange solution was stirred at −78° C. for 5 min, then EtI (0.045 mL, 0.563 mmol) was added. The reaction was stirred and allowed to slowly warm to −30° C. over 45 min. Additional LiHMDS (IM in THF, 0.250 mL, 0.250 mmol) and EtI (0.025 mL) were added and the mixture was allowed to warm to −20° C. over 30 min. The reaction was quenched with the addition of sat. NH4Cl. The mixture was diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (40 to 45% EtOAc/hexanes) to afford 81.1 mg (72%) of 37a as a colorless foam. MS (ESI) 501.3 (M+H+), 523.3 (M+Na+), 499.4 (M−H+), 535.3 (M+Cl−).

Workup

  1. stirringThe reaction was stirred
  2. temperatureto slowly warm to −30° C. over 45 min
  3. temperatureto warm to −20° C. over 30 min
  4. customThe reaction was quenched with the addition of sat. NH4Cl
  5. additionThe mixture was diluted with EtOAc
  6. washThe organic phase was washed with H2O and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography (40 to 45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-099639eee6ab4646a8db056db0679e3a
Source dataset
uspto-grants-2006_08
Patent number
US07094783B2

Linked notes

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