Bromomethylstyrene → Benzyl (6S,8R)-6-(anilinocarbonyl)-8-methyl-4-oxo-8-[(2E)-3-phenyl-2-propenyl]-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidin-3-yl(benzyl)carbamate

HRID 481253Notes

Reaction equation

HRID 481253 reaction equation
[NH:1]([C:8]([C@H:10]1[N:14]2[C:15](=[O:41])[C:16]([N:19]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33](C(F)(F)F)[CH:32]=3)[C:20](=[O:29])[O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:17][N:18]=[C:13]2[CH:12]([CH3:42])[CH2:11]1)=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:53](Br)[CH:54]=[CH:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1>C1COCC1>[NH:1]([C:8]([C@H:10]1[N:14]2[C:15](=[O:41])[C:16]([N:19]([CH2:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:20](=[O:29])[O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[CH:17][N:18]=[C:13]2[C@:12]([CH3:42])([CH2:53]/[CH:54]=[CH:55]/[C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[CH2:11]1)=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 98116BromomethylstyreneHCID 2733832Lithium HexamethyldisilazideHCID 86587570Benzyl (6S,8RS)-6-(anilinocarbonyl)-8-methyl-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidin-3-yl[3-(trifluoromethyl)benzyl]carbamate

Product 1

HCID 86587574Benzyl (6S,8R)-6-(anilinocarbonyl)-8-methyl-4-oxo-8-[(2E)-3-phenyl-2-propenyl]-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidin-3-yl(benzyl)carbamateYield 66.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 12c (32 mg, 0.063 mmol) in 1 mL THF at −78° C., was added LiHMDS (157 μL, 0.157 mmol). The mixture was stirred at −78° C. for 10 min, then cinnamyl bromide (18.6 mg, 0.095 mmol) in 250 μL THF was added. The reaction was stirred at −78° C. for 1.5 h, then quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with sat NH4Cl and brine, dried (Na2SO4), and concentrated. The crude mixture was purified by flash chromatography (35% EtOAc/hexanes) to afford 26.0 mg (66%) of 116a. 1H NMR (300 MHz, CDCl3) δ9.57 (br s, 1H), 7.74 (br s, 1H), 7.47 (d, J=8.1, 2H), 7.29-7.23 (m, 17H), 7.07 (t, J=7.5, 1H), 6.47 (d, J=15.7, 1H), 6.02-5.97 (m, 1H), 5.20-5.17 (m, 3H), 4.80 (br s, 1H), 2.70-2.41 (m, 4H), 1.48 (s, 3H).

Workup

  1. stirringThe reaction was stirred at −78° C. for 1.5 h
  2. customquenched with sat. NH4Cl
  3. additionThe mixture was diluted with EtOAc
  4. washwashed
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude mixture was purified by flash chromatography (35% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0aa4e14e7208457fa3ad0e51bf5f5c0a
Source dataset
uspto-grants-2003_11
Patent number
US06653295B2

Reaction notes

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