Trifluoroacetic acid → HCID 58048576, compound

HRID 2043237Notes

Reaction equation

HRID 2043237 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>C(Cl)Cl>[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

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86660892HCID 86660892, compound

Product 2

HCID 58048576HCID 58048576, compoundHCID 58048588HCID 58048588, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 CH2Cl2 (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 1 N 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 1 N 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-bf05da6ef1c443c986643d6bd6bfcb0d
Source dataset
uspto-grants-2013_11
Patent number
US08586615B2

Reaction notes

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