Benzyl Bromide → HCID 9861558, compound

HRID 392644Notes

Reaction equation

HRID 392644 reaction equation
Cl.[NH2:2][CH2:3][C@@H:4]1[O:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]3[NH:16][C:15](=[O:17])[O:14][C:11]3=2)[O:6][CH2:5]1.[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(CC)C(C)C)(C)C>CS(C)=O>[CH2:18]([NH:2][CH2:3][CH:4]1[O:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]3[NH:16][C:15](=[O:17])[O:14][C:11]3=2)[O:6][CH2:5]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 81531DiisopropylethylamineHCID 69920517HCID 69920517, compound

Product 1

HCID 9861558HCID 9861558, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

(8S)-8-Aminomethyl-7,8-dihydro-3H-1,6,9-trioxa-3-aza-cyclopenta[a]-naphthalen-2-one hydrochloride (0.49 g, 1.8 mmole), benzyl bromide (0.20 mL, 1.8 mmole) and 0.31 mL (1.8 mmole) of N,N-diisopropylethylamine were combined in 20 ml DMSO and heated at 50° C. under nitrogen for 6 hours. After completion, the reaction was cooled to room temperature and partitioned between 400 mL each of ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was removed and washed with brine, dried over magnesium sulfate and concentrated in vacuum. The crude residue was column chromatographed on silica gel using first methylene chloride, then 1% methanol in methylene chloride to elute the dialkylated product and finally 3% methanol in methylene chloride to elute the monoalkylated product (0.16 g, 28%). The latter was recrystallized from ethanol with the addition of a solution of fumaric acid (0.065 g) in hot ethanol to give 0.06 g of the (S)-enantiomer of the title compound as an off-white solid hemifumarate, one-quarter hydrate, m.p. 220° C.

Workup

  1. temperatureAfter completion, the reaction was cooled to room temperature
  2. custompartitioned between 400 mL each of ethyl acetate and saturated aqueous sodium bicarbonate
  3. customThe organic phase was removed
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuum
  7. customchromatographed on silica gel using first methylene chloride
  8. wash1% methanol in methylene chloride to elute the dialkylated product and finally 3% methanol in methylene chloride
  9. washto elute the monoalkylated product (0.16 g, 28%)
  10. customThe latter was recrystallized from ethanol with the addition of a solution of fumaric acid (0.065 g) in hot ethanol

Sources & evidence

ORD record
ord-6c81930451774a74be8f23bec95b66d7
Source dataset
uspto-grants-2004_10
Patent number
US06800648B2

Reaction notes

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