Hydrochloric Acid → HCID 57959865, compound

HRID 1698501Notes

Reaction equation

HRID 1698501 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.CO[N:13](C)[C:14]([CH:16]1[CH:21]2[CH2:22][CH:18]([CH2:19][CH2:20]2)[N:17]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=O.Cl.[C:32]([S:36](N)=[O:37])([CH3:35])([CH3:34])[CH3:33]>C1(C)C=CC=CC=1.C(OCC)C.[Cl-].[Na+].O.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC.C(OCC)(=O)C.C1COCC1.CCCCCC>[C:32]([S:36](/[N:13]=[CH:14]/[CH:16]1[CH:21]2[CH2:22][CH:18]([CH2:19][CH2:20]2)[N:17]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:37])([CH3:35])([CH3:34])[CH3:33]

Participants

12

Reactant 4

HCID 313Hydrochloric AcidHCID 3382465Tert-ButanesulfinamideHCID 21225700DiisobutylaluminumhydrideHCID 57959898HCID 57959898, compound

Product 1

HCID 57959865HCID 57959865, compoundYield 85.6%

Reagents, catalysts & solvents 7

HCID 76524Titanium tetraethoxideCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

Diisobutylaluminium hydride (50 mL of a 1M solution in toluene, 50 mmol) was added to a pre-cooled (−78° C.) solution of tert-butyl 3-{[methoxy(methyl)amino]-carbonyl}-2-azabicyclo[2.2.1]heptane-2-carboxylate (6.17 g, 21.7 mmol) in diethyl ether (80 mL). The mixture was stirred at −78° C. for 2 hours and then at 0° C. for 10 min. The reaction was poured into a mixture of 1N hydrochloric acid (180 mL), diethyl ether (150 mL) and hexane (150 mL) and stirred for 20 min. The organic layer was washed with brine, dried Na2SO4) and concentrated. The residue was treated with THF (90 mL), tert-butylsulphinamide (3.15 g, 26 mmol) and titanium ethoxide (9.1 mL, 43.4 mmol) and stirred at ambient temperature for 12 h. The mixture was treated with brine (120 mL) and ethyl acetate (150 mL) and stirred for 30 min. The organic phase was removed and retained. The aqueous residue was washed with 2 further portions of ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified on a pad of silica gel eluting with iso-hexane containing 0.5% triethylamine on a gradient of ethyl acetate (0-40%) to give the title product (6.1 g, 85%). 1H NMR (400 MHz, CDCl3): δ 7.94-7.88 (1H, m), 4.33 (0.5H, s), 4.22 (0.5H, s), 4.10 (0.5H, m), 4.02 (0.5H, m), 2.75-2.65 (1.5H, m), 2.58 (0.5H, d, J=5.5), 1.88-1.50 (4H, m), 1.48-1.38 (9H, m), 1.34-1.26 (2H, m), 1.24-1.20 (9H, m).

Workup

  1. waitat 0° C. for 10 min
  2. stirringstirred for 20 min
  3. washThe organic layer was washed with brine, dried Na2SO4) and
  4. concentrationconcentrated
  5. stirringstirred at ambient temperature for 12 h
  6. stirringstirred for 30 min
  7. customThe organic phase was removed
  8. washThe aqueous residue was washed with 2 further portions of ethyl acetate
  9. dry with materialThe combined organic extracts were dried (Na2SO4)
  10. concentrationconcentrated
  11. customThe residue was purified on a pad of silica gel eluting with iso-hexane containing 0.5% triethylamine on a gradient of ethyl acetate (0-40%)

Sources & evidence

ORD record
ord-d5253da76084477e841f9e76446026c2
Source dataset
uspto-grants-2012_04
Patent number
US08163956B2

Reaction notes

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