Ammonium Chloride → HCID 67394233, compound

HRID 588487Notes

Reaction equation

HRID 588487 reaction equation
[C:1]([S@@:5](/[N:7]=[CH:8]/[C:9]1[S:13][C:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:11][CH:10]=1)=[O:6])([CH3:4])([CH3:3])[CH3:2].[CH3:21][Mg]Br.[NH4+].[Cl-]>C(Cl)Cl>[C:17]([O:16][C:14]([C:12]1[S:13][C:9]([C@H:8]([NH:7][S@:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[O:6])[CH3:21])=[CH:10][CH:11]=1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 87383933HCID 87383933, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 67394233HCID 67394233, compoundYield 48.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-45 °C

Procedure

To an oven-dried 100-mL round-bottom flask was added (S,E)-tert-butyl 5-((tert-butylsulfinylimino)methyl)thiophene-2-carboxylate (1.00 g, 3.2 mmol) and DCM (15.8 mL). The solution was cooled to −45° C. under nitrogen, then methylmagnesium bromide (2.11 mL, 6.36 mmol, 3.0 M in ether) was slowly added via syringe. The resulting reaction mixture was stirred at −45° C. for 4 h, then gradually warmed to rt and stirred for 2 h. To the reaction was added DCM (50 mL) and sat. NH4Cl solution (10 mL). After separation, the aqueous layer was extracted with DCM (2×30 mL). The combined organic layers were washed with brine, dried (MgSO4), and concentrated. Purification via flash chromatography (20% EtOAc-hexanes to 50% EtOAc-hexanes) afforded major diastereomer tert-butyl-5-[(1R)-1-{[(S)-tert-butylsulfinyl]amino}ethyl]thiophene-2-carboxylate (0.51 g, 48%) as a white solid; 1H NMR (Methanol-d4, 400 MHz) δ 7.55 (d, J=3.8 Hz, 1H), 7.00 (d, J=3.8 Hz, 1H), 4.73 (q, J=6.5 Hz, 1H), 3.30 (br, 1H), 1.65 (d, J=6.8 Hz, 3H), 1.55 (s, 9H), 1.25 (s, 9H). Minor diastereomer tert-butyl-5-[(1S)-1-{[(S)-tert-butylsulfinyl]amino}ethyl]thiophene-2-carboxylate (0.061 g, 6%) was isolated as a white solid. 1H NMR (Methanol-d4, 400 MHz) δ 7.55 (d, J=3.5 Hz, 1H), 7.00 (d, J=3.5 Hz, 1H), 4.73 (q, J=6.8 Hz, 1H), 3.30 (br, 1H), 1.61 (d, J=6.8 Hz, 3H), 1.55 (s, 9H), 1.23 (s, 9H).

Workup

  1. customThe resulting reaction mixture
  2. temperaturegradually warmed to rt
  3. stirringstirred for 2 h
  4. customAfter separation
  5. extractionthe aqueous layer was extracted with DCM (2×30 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customPurification via flash chromatography (20% EtOAc-hexanes to 50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-86b3f1e496394eb9995c169d05bca728
Source dataset
uspto-grants-2016_01
Patent number
US09227951B2

Reaction notes

Loading…