HCID 57959883, compound → HCID 86635957, compound

HRID 1698498Notes

Reaction equation

HRID 1698498 reaction equation
[CH2:1]([S:3][C:4]1[CH:5]=[C:6]([Mg]Br)[CH:7]=[CH:8][CH:9]=1)[CH3:2].C(S(/[N:18]=[CH:19]\[CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=O)(C)(C)C>C1COCC1>[NH2:18][CH:19]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([S:3][CH2:1][CH3:2])[CH:5]=1)[CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27]

Participants

4

Reactant 2

HCID 57959883HCID 57959883, compoundHCID 178477277HCID 178477277, compound

Product 1

HCID 86635957HCID 86635957, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3-(ethylthio)phenylmagnesium bromide in THF (10 mL 11.6 mmol) was added to a cooled (0° C.) solution of tert-butyl 2-{(Z)-[(tert-butylsulfinyl)imino]methyl}piperidine-1-carboxylate (1.5 g, 4.7 mmol) in THF (10 mL) and the mixture was stirred for 60 min The mixture was quenched with 50 mL of a 1:1 mixture of saturated aqueous ammonium chloride and 33% aqueous ammonia before extracting into ethyl acetate (100 mL). The organic phase was dried (MgSO4) and concentrated. The residue was treated with methanol (20 mL), cooled to 0° C. and then 4N hydrogen chloride in dioxane (5 mL) was added. After stirring for 30 min 4N aqueous sodium hydroxide (6 mL) was added and the mixture was extracted into DCM. The organic extract was dried (Na2SO4) and concentrated. The residue was purified on silica gel eluting with iso-hexane on a gradient of ethyl acetate (0-60%) followed by dichloromethane on a gradient of methanol (2-10%) to give the title product as a 1.7:1 mixture of diastereoisomers (860 mg, 51%). 1H NMR (360 MHz, CDCl3): δ 7.30-7.09 (4H, m), 4.30-4.1 (2H, m), 4.05-3.88 (1H, br), 3.78-3.60 (2H, m), 2.99-2.88 (2H, m), 2.80 (1H, dt, J=2.8, 13.4 Hz), 2.11 (1H, d, J=13.6 Hz), 1.75-1.41 (5H, m), 1.34-1.30 (3H, m), 1.23 (3.5H, s), 1.20 (5.5H, s).

Workup

  1. customwas quenched with 50 mL of a 1:1 mixture of saturated aqueous ammonium chloride and 33% aqueous ammonia
  2. extractionbefore extracting into ethyl acetate (100 mL)
  3. dry with materialThe organic phase was dried (MgSO4)
  4. concentrationconcentrated
  5. additionThe residue was treated with methanol (20 mL)
  6. addition4N hydrogen chloride in dioxane (5 mL) was added
  7. stirringAfter stirring for 30 min 4N aqueous sodium hydroxide (6 mL)
  8. additionwas added
  9. extractionthe mixture was extracted into DCM
  10. extractionThe organic extract
  11. dry with materialwas dried (Na2SO4)
  12. concentrationconcentrated
  13. customThe residue was purified on silica gel eluting with iso-hexane on a gradient of ethyl acetate (0-60%)

Sources & evidence

ORD record
ord-d381d140ba424adcb7fe3a996b0fcdce
Source dataset
uspto-grants-2012_04
Patent number
US08163956B2

Reaction notes

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