1,1-Dibromoethane → HCID 89657462, compound

HRID 1775239Notes

Reaction equation

HRID 1775239 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[C:3]=1[C:12]#[C:13][C@@:14]1([CH3:29])[CH2:18][CH2:17][CH2:16][N:15]1[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20].BrC(Br)C>C(O)C.[Zn]>[CH2:22]([O:21][C:19]([N:15]1[CH2:16][CH2:17][CH2:18][C@@:14]1([C:13]1[NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[C:3]=2[CH:12]=1)[CH3:29])=[O:20])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 2

HCID 112011,1-DibromoethaneHCID 131734732HCID 131734732, compound

Product 1

HCID 89657462HCID 89657462, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 702EthanolSolvent

Procedure

To a refluxing solution of (R)-benzyl 2-((2-amino-6-(methoxycarbonyl)phenyl)ethynyl)-2-methylpyrrolidine-1-carboxylate (1.1 g, 2.8 mmol) and dibromoethane (5.21 g, 2.8 mmol) in ethanol (20 mL) was added zinc powder (1.43 g, 22 mmol) in one portion. After refluxing for 8 h, the reaction mixture was filtered and the the filtrate was concentrated to 3 mL, which was poured into water (15 mL). The reaction mixture was extracted with EA (20 mL×3). The combined extracts were dried over sodium sulfate, filtered, and evaporated to give pale brown oil, which was chromatographed over silica gelelution with hexane:ethyl acetate (5:1) to give the (R)-methyl 2-(1-(benzyloxycarbonyl)-2-methylpyrrolidin-2-yl)-1H-indole-4-carboxylate and (307 mg, 0.78 mmol). 1H NMR (CDCl3-d) δ 10.3 (s, 1H), 7.83 (d, 1H, J=7.8 Hz), 7.53 (d, 1H, J=7.8 Hz), 7.29-7.35 (m, 5H), 7.16 (t, 1H, J=7.8 Hz), 6.96 (s, 1H), 5.15 (s, 2H), 3.95 (s, 3H), 3.56-3.59 (m, 2H), 2.83-2.85 (m, 1H), 2.03-2.07 (m, 2H), and 1.84-1.93 (m, 4H). MS (ESI) m/e [M+1]+ 393.0.

Workup

  1. temperatureAfter refluxing for 8 h
  2. filtrationthe reaction mixture was filtered
  3. concentrationthe the filtrate was concentrated to 3 mL, which
  4. additionwas poured into water (15 mL)
  5. extractionThe reaction mixture was extracted with EA (20 mL×3)
  6. dry with materialThe combined extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto give pale brown oil, which
  10. customwas chromatographed over silica gelelution with hexane:ethyl acetate (5:1)

Sources & evidence

ORD record
ord-2af16011c65546b0a3781090dc3ae146
Source dataset
uspto-grants-2016_02
Patent number
US09260440B2

Reaction notes

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