Trifluoroacetic acid → HCID 58048576, compound

HRID 530005Notes

Reaction equation

HRID 530005 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:8]([NH:23][S:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[C:9]1[S:13][C:12]([NH:14]C(=O)OC(C)(C)C)=[N:11][C:10]=1[CH3:22].C(O)(C(F)(F)F)=O>>[NH2:14][C:12]1[S:13][C:9]([C@@H:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[NH:23][S@@:24]([C:26]([CH3:29])([CH3:27])[CH3:28])=[O:25])=[C:10]([CH3:22])[N:11]=1.[NH2:14][C:12]1[S:13][C:9]([C@H:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[NH:23][S@@:24]([C:26]([CH3:29])([CH3:27])[CH3:28])=[O:25])=[C:10]([CH3:22])[N:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86660892HCID 86660892, compound

Product 2

HCID 58048576HCID 58048576, compoundHCID 58048588HCID 58048588, compound

Procedure

To a solution of (R)-tert-Butyl 5-((2-chlorophenyl)(1,1-dimethylethylsulfinamido)methyl)-4-methylthiazol-2-ylcarbamate, (19.0 g, 41.6 mmol) in CH2Cl3 (83 mL) was added TFA (83 mL). The reaction was stirred at room temperature for 1 h. The reaction was concentrated and then partitioned between CH2Cl2 and saturated aqueous NaHCO3 solution. The aqueous layer was basified to pH>12 by adding 1N NaOH solution and extracted with Ch2Cl2. The combined organic layers were dried over MgSO4 and concentrated. The crude product was adsorbed onto silica gel and purified by column chromatography (70-100% EtOAc/hexanes. The EtOAc contained 2% NH4OH and was stirred to maintain the mixture) to provide (R)-N-((R)-(2-amino-4-methylthiazol-5-yl)(2-chlorophenyl)methyl)-2-methylpropane-2-sulfinamide and (R)-N-((S)-(2-amino-4-methylthiazol-5-yl)(2-chlorophenyl)methyl)-2-methylpropane-2-sulfinamide and a mixture of both diastereomers (7.1 g, 47%). First eluted product (Isomer A) (white solid, 3.0 g, 20%, >99% de); 1H NMR (400 MHz, CDCl3) δ 7.60 (dd, J=1.6, 7.7 Hz, 1H), 7.38-7.22 (m, 3H), 6.15 (d, J=2.5 Hz, 1H), 4.94 (s, 2H), 3.87 (d, J=2.3 Hz, 1H), 2.34 (s, 3H), 1.27 (s, 9H); HPLC ret. time 3.08 min, 10-99% CH3CN, 15 min run; ESI-MS 358.3 m/z (MH+). Second eluted product (Isomer B) (yellow waxy solid, 5.0 g, 33% 98% de); 1H NMR (400 MHz, CDCl3) δ 7.64 (dd, J=7.7, 1.7 Hz, 1H), 7.36 (dd, J=7.8, 1.4 Hz, 1H), 7.32-7.21 (m, 2H), 6.19 (d, J=1.8 Hz, 1H), 4.86 (s, 2H), 3.65 (d, J=1.2 Hz, 1H), 2.33 (s, 3H), 1.26 (s, 9H); HPLC ret. time 3.77 min, 10-99% CH3CN, 15 min run; ESI-MS 358.3 m/z (MH+).

Workup

  1. concentrationThe reaction was concentrated
  2. custompartitioned between CH2Cl2 and saturated aqueous NaHCO3 solution
  3. additionby adding 1N NaOH solution
  4. extractionextracted with Ch2Cl2
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. custompurified by column chromatography (70-100% EtOAc/hexanes
  8. stirringwas stirred
  9. temperatureto maintain the mixture)

Sources & evidence

ORD record
ord-d0ebb2cbe52c4d94b35f3466f78c8310
Source dataset
uspto-grants-2016_05
Patent number
US09351962B2

Reaction notes

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