Trifluoroacetic acid → HCID 66853777, compound

HRID 876357Notes

Reaction equation

HRID 876357 reaction equation
[C:1]([O:4][CH:5]1[CH2:9][N:8]([C:10](=[O:22])[CH:11]([NH:14]C(OC(C)(C)C)=O)[CH2:12][CH3:13])[CH:7]([CH2:23][C:24]2[C:32]3[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=3)[NH:26][C:25]=2[C:34]2[NH:35][C:36]3[C:41]([C:42]=2[CH2:43][CH:44]2[N:48]([C:49](=[O:61])[CH:50]([NH:53]C(OC(C)(C)C)=O)[CH2:51][CH3:52])[CH2:47][CH:46]([O:62][C:63](=[O:65])[CH3:64])[CH2:45]2)=[CH:40][CH:39]=[C:38]([F:66])[CH:37]=3)[CH2:6]1)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([O:4][CH:5]1[CH2:9][N:8]([C:10](=[O:22])[CH:11]([NH2:14])[CH2:12][CH3:13])[CH:7]([CH2:23][C:24]2[C:32]3[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=3)[NH:26][C:25]=2[C:34]2[NH:35][C:36]3[C:41]([C:42]=2[CH2:43][CH:44]2[N:48]([C:49](=[O:61])[CH:50]([NH2:53])[CH2:51][CH3:52])[CH2:47][CH:46]([O:62][C:63](=[O:65])[CH3:64])[CH2:45]2)=[CH:40][CH:39]=[C:38]([F:66])[CH:37]=3)[CH2:6]1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 75577552HCID 75577552, compound2×

Product 1

HCID 66853777HCID 66853777, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution containing 11 (27.5 g, 30 mmol) in DCM (200 mL) was cooled to 0° C. TFA (50 mL) was added and the reaction was monitored by LC/MS analysis until complete conversion of 11 to 12 (ca. 3 h). The solvent was removed in vacuo and the dark, green-colored residue was dissolved in EtOAc (ca. 1 L). The EtOAc solution was carefully poured into a saturated aqueous NaHCO3/ice/water mixture to neutralize the residual TFA. The organic phase was separated and washed twice with saturated aqueous NaHCO3 then once with brine. The combined aqueous washes were back-extracted with EtOAc (2×100 mL) and the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated to afford 22 g of crude 12 as an off-white solid. 1H NMR (300 MHz, CDCl3+d4-MeOH), mixture of rotomers: δ11.62 (br s, 2H), 7.48-7.62 (m, 4H), 6.89 (ddd, J=2.4, 9.3, 9.3 Hz, 2H), 5.48 (dd, J=4.5, 4.8 Hz, 2H), 4.52 (dd, J=9.3, 9.3 Hz, 2H), 4.06 (dd, J=4.8, 12.3 Hz, 2H), 3.78 (d, J=12.3 Hz, 2H), 3.54-3.70 (m, 4H), 3.30-3.40 (m, 2H), 2.33 (s, 6H), 2.02-2.16 (m, 2H), 1.70-1.96 (m, 4H), 1.09 (t, J=7.2 Hz, 6H) ppm; 13C NMR (75 MHz, CDCl3+d4-MeOH): 8173.5, 170.9, 161.8, 158.6, 137.2, 137.1, 128.2, 128.1, 125.6, 118.7, 118.6, 108.6, 108.3, 108.0, 98.6, 98.1, 74.6, 60.1, 53.5, 33.5, 28.0, 21.4, 9.7 ppm. Mass spectrum (ESI), m/z 721.4 [(M)+; calcd for C38H46F2N6O6: 720.8].

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe dark, green-colored residue was dissolved in EtOAc (ca. 1 L)
  3. additionThe EtOAc solution was carefully poured into a saturated aqueous NaHCO3/ice/water mixture
  4. customThe organic phase was separated
  5. washwashed twice with saturated aqueous NaHCO3
  6. extractionThe combined aqueous washes were back-extracted with EtOAc (2×100 mL)
  7. dry with materialthe combined organic extracts were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c278a72a467d4d028572ac6358bbdfee
Source dataset
uspto-grants-2015_03
Patent number
US08986993B2

Reaction notes

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