Formic Acid → HCID 178448486, compound

HRID 340643Notes

Reaction equation

HRID 340643 reaction equation
[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11]([C:13]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:14]=2[O:15][CH2:16][C@@H:17]2[CH2:20][CH2:19][N:18]2[C:21](OC(C)(C)C)=O)=[O:12])/[N:7]([CH2:36][CH:37]([CH3:39])[CH3:38])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C=O.C(O)=O.[C:45]1([CH3:55])[CH:50]=[CH:49][C:48]([S:51]([OH:54])(=[O:53])=[O:52])=[CH:47][CH:46]=1.O>CCOC(C)=O>[C:45]1([CH3:55])[CH:46]=[CH:47][C:48]([S:51]([OH:54])(=[O:52])=[O:53])=[CH:49][CH:50]=1.[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:12])[C:13]2[CH:31]=[C:30]([C:32]([F:34])([F:33])[F:35])[CH:29]=[CH:28][C:14]=2[O:15][CH2:16][C@@H:17]2[CH2:20][CH2:19][N:18]2[CH3:21])/[N:7]([CH2:36][CH:37]([CH3:39])[CH3:38])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 712FormaldehydeHCID 521998p-Toluenesulfonic acid monohydrateHCID 178448487HCID 178448487, compound

Product 2

HCID 6101p-Toluenesulfonic acidHCID 178448486HCID 178448486, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of the product of Example 12B (0.45 g, 0.79 mmol) in formaldehyde (2 mL, 72.6 mmol) and formic acid (4 mL, 104 mmol) was warmed to 100° C. and was allowed to stir for 2 h then was cooled to ambient temperature and was concentrated under reduced pressure. The mixture was purified via column chromatography (SiO2, 100% CH2Cl2 to 9:1:0.1 CH2Cl2:CH3OH:NH4OH). The free amine was dissolved in EtOAc (1 mL) and p-toluenesulfonic acid-H2O (1 eq) in EtOAc (1 mL) was added. The p-toluenesulfonic acid salt of the title compound (0.25 g, 0.38 mmol, 48% yield) was isolated via filtration. 1H NMR (300 MHz, CD3OD) δ ppm 0.98 (dd, J=6.6, 2.2 Hz, 6H), 1.39 (s, 9H), 2.27-2.34 (m, 1H), 2.36 (s, 3H), 2.55-2.76 (m, 2H), 3.06 (s, 3H), 3.98-4.18 (m, 3H), 4.26-4.37 (m, 1H), 4.50 (d, J=3.4 Hz, 2H), 4.73-4.80 (m, 1H), 7.19-7.26 (m, 3H), 7.34 (d, J=8.8 Hz, 1H), 7.67-7.73 (m, 2H), 7.79 (dd, J=8.8, 2.0 Hz, 1H), 8.39 (d, J=2.0 Hz, 1H); MS (DCI/NH3) m/z 484 (M+H)+. Anal. calculated for C24H32F3N3O2S.C7H8O3S.0.2H2O: Calc: C, 56.47; H, 6.18; N, 6.37. Found: C, 56.19; H, 6.28; N, 6.38.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customThe mixture was purified via column chromatography (SiO2, 100% CH2Cl2 to 9:1:0.1 CH2Cl2:CH3OH:NH4OH)
  3. dissolutionThe free amine was dissolved in EtOAc (1 mL)

Sources & evidence

ORD record
ord-4e73abb09cb8460d8a75b1592245e9a9
Source dataset
uspto-grants-2014_11
Patent number
US08895592B2

Reaction notes

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