Methanol → HCID 178455592, compound

HRID 2278370Notes

Reaction equation

HRID 2278370 reaction equation
[Si:1]([O:8][CH2:9]/[CH:10]=[N:11]/[S:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(Cl)Cl.[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[Li].CO>[NH4+].[Cl-]>[CH3:5][C:4]([CH3:7])([Si:1]([CH3:3])([CH3:2])[O:8][CH2:9][C@H:10]([C:22]1[S:21][CH:25]=[CH:24][CH:23]=1)[NH:11][S+:12]([O-:13])[C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:6]

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 87221168HCID 87221168, compoundHCID 178418439HCID 178418439, compound

Product 1

HCID 178455592HCID 178455592, compound

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Procedure

A three necked round bottom flask fitted with a temperature probe, nitrogen inlet, mechanical stirrer and slow addition funnel was charged with N-[(1E)-2-{[tert-butyl(dimethyl)silyl]oxy}ethylidene]-2-methylpropane-2-sulfinamide (176 g, 0.530 mol) and DCM (2 L). At an internal temperature of −65° C., 2-thienyl lithium (1.0 M in THF) (0.794 L, 0.794 mol) was added dropwise such that the internal temperature was maintained <−65° C. The reaction mixture was stirred for 60 minutes, quenched at −65° C. with methanol (0.214 L, 5.30 mol), diluted with NH4Cl (2 L) and warmed to room temperature. The layers were then separated and the aqueous layer was back extracted with DCM (2 L). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude concentrate was pre-loaded onto silica, divided into 4 batches, and purified by automated flash chromatography (4×1.5 kg SiO2 columns, hexanes:EtOAc; 5% to 50% gradient over to provide the title compound as an amber oil. 1H NMR ((CD3)2CO) δ 7.42 (1H, d, J=4.0 Hz), 7.14 (1H, s), 7.01 (1H, J=4.0, 3.5 Hz), 4.78-4.75 (1H, m), 4.48 (1H, s), 3.95-3.92 (1H, m), 3.86-3.82 (1H, m), 1.23 (9H, s), 0.94 (9H, s), 0.12 (6H, s).

Workup

  1. customA three necked round bottom flask fitted with a temperature probe, nitrogen inlet, mechanical stirrer and slow addition funnel
  2. temperaturewas maintained <−65° C
  3. customThe layers were then separated
  4. extractionthe aqueous layer was back extracted with DCM (2 L)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. concentrationThe crude concentrate
  9. custompurified by automated flash chromatography (4×1.5 kg SiO2 columns, hexanes

Sources & evidence

ORD record
ord-ae1cf7b7af18438484fddb6a97be8086
Source dataset
uspto-grants-2015_09
Patent number
US09133157B2

Reaction notes

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