Sodium → HCID 21931720, compound

HRID 1244036Notes

Reaction equation

HRID 1244036 reaction equation
C1(S([CH:10]2[CH2:16][C:15]3([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:17]([CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:11]2[CH2:12][CH2:13][CH:14]3[NH:31]OC)(=O)=O)C=CC=CC=1.[Na]>C1COCC1>[CH2:18]([N:17]1[CH:11]2[CH2:10][CH2:16][C:15]1([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH:14]([NH2:31])[CH2:13][CH2:12]2)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 5360545SodiumHCID 21931703HCID 21931703, compound

Product 1

HCID 21931720HCID 21931720, compoundYield 69.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A flame dried 3/N round bottom flask equipped with an NH3 (g) inlet, dry ice condenser and magnetic stir bar was cooled to −78° C. and ammonia gas was introduced. A solution of 464 mg (1.0 mmol) of the N-(6-Benzenesulfonyl-8-benzyl-1-phenyl-8-aza-bicyclo[3.2.1]oct-2-yl)-O-methyl-hydroxylamine in 10 ml of THF was added followed by 323 mg (14.05 mmol) sodium metal portionwise. A deep blue color was evident and the reaction mixture was stirred at −78° C. for 30 min. The reaction was quenched by the addition of solid ammonium chloride and the ammonia was allowed to evaporate. The residue was taken up in water and methylene chloride. The aqueous phase was washed once again with methylene chloride. The combined organic layers were washed with brine, dried of sodium sulfate and evaporated in vacuo. There was obtained 203 mg (68%) of a clear oil. Enantiomeric separation was completed on a 5 cm×50 cm Chirlpak AS column eluting at 25 ml/min with 93/7 hexane/ethanol containing 0.025% diethyl amine. The retention times were 4.6 minutes and 6.6 minutes respectively. 1H NMR (CDCl3, 400 MHz) δ 7.49–7.41 (m, 2H), 7.37–7.27 (br.m., 5H), 7.24–7.18 (br.m., 3H), 3.97 (d, 1H, J=15 Hz), 3.26–3.24 (br.s., 1H), 2.97 (d, 1H, J=15 Hz), 2.54–2.53 (br.s., 1H), 2.40 (br.s., 2H), 2.33–2.15 (br.m., 3H), 2.03–1.86 (br.m., 2H), 1.72–1.64 (br.m., 2H), 1.33–1.28 (br.m., 1H) ppm. Mass spectrum APCI m/z 293 (p+1).

Workup

  1. customA flame dried 3/N round bottom flask
  2. customequipped with an NH3 (g) inlet, dry ice condenser and magnetic stir bar
  3. additionammonia gas was introduced
  4. customThe reaction was quenched by the addition of solid ammonium chloride
  5. customto evaporate
  6. washThe aqueous phase was washed once again with methylene chloride
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried of sodium sulfate
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-d1a542ff27884807bf732088cca7c959
Source dataset
uspto-grants-2006_10
Patent number
US07119207B2

Reaction notes

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