Trifluoroacetic acid → HCID 67408937, compound

HRID 1949658Notes

Reaction equation

HRID 1949658 reaction equation
C(O)(C(F)(F)F)=O.[CH2:8]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH:20]2[N:23]([C:26](=[O:48])[CH:27]([NH:34][C:35](=[O:47])[CH:36]([N:38](C(OC(C)(C)C)=O)[CH3:39])[CH3:37])[CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[CH2:24][CH2:25][CH:19]12)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(Cl)Cl>[CH2:8]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH:20]2[N:23]([C:26](=[O:48])[CH:27]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[NH:34][C:35](=[O:47])[CH:36]([NH:38][CH3:39])[CH3:37])[CH2:24][CH2:25][CH:19]12)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 67408517HCID 67408517, compound

Product 1

HCID 67408937HCID 67408937, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (5 mL) was added to a solution containing crude 116 (0.9 g) in DCM (20 mL) at 0° C. After 90 min, another portion of TFA (2 mL) was added. After 75 min, the reaction mixture was carefully quenched by the addition of saturated aqueous NaHCO3. The mixture was then diluted with EtOAc and water and the layers were separated. The organic phase was washed three times with aqueous NaHCO3 then once with brine. The combined aqueous washes were back-extracted with EtOAc and the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by reverse-phase HPLC [2″ Dynamax C18; Method: 10-55% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min]. The product-containing fractions were pooled, frozen, and lyophilized to afford 410 mg (53% from 115) of 117 as a white-colored solid. 1H NMR (300 MHz, d6-DMSO), mixture of carbamate rotomers: δ7.67 (d, J=8.7 Hz, 1H), 7.34-7.28 (m, 5H), 5.17-5.05 (m, 2H), 4.52 (m, 2H), 4.34 (m, 1H), 4.00 (m, 1H), 3.75 (m, 1H), 3.33 (m, 1H), 3.14-3.01 (m, 2H), 2.35 (br s, 3H), 2.30 (m, 1H), 1.90 (m, 1H), 1.69-1.60 (m, 5H), 1.27 (d, J=6.9 Hz, 3H), 1.18-0.94 (m, 5H) ppm. 13C NMR (75 MHz, d6-DMSO), mixture of carbamate rotomers: δ174.7, 174.4 172.9, 170.1, 170.0, 154.1, 154.0, 137.5, 129.1, 128.5, 128.2, 128.1, 66.7, 66.6, 63.0, 61.9, 61.6, 60.9, 59.5, 55.2, 54.7, 46.7, 46.1, 45.6, 41.5, 34.5, 32.3, 31.2, 30.7, 30.1, 29.6, 29.5, 28.9, 28.7, 26.4, 26.2, 26.1, 26.0, 22.0, 19.5, 19.4 ppm. Mass spectrum, m/z [471.0] (M+H)+.

Workup

  1. waitAfter 75 min
  2. customthe reaction mixture was carefully quenched by the addition of saturated aqueous NaHCO3
  3. additionThe mixture was then diluted with EtOAc and water
  4. customthe layers were separated
  5. washThe organic phase was washed three times with aqueous NaHCO3
  6. extractionThe combined aqueous washes were back-extracted with EtOAc
  7. dry with materialthe combined organic extracts were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by reverse-phase HPLC [2″ Dynamax
  11. waitMethod: 10-55% ACN/water containing 0.1% HOAc over 30 min
  12. temperaturefrozen

Sources & evidence

ORD record
ord-5175b26e02e54b9490328aadfa8c4643
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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