Reaction SMILES: Cl[C:2]1C=CC(C=O)=CC=1.[CH3:10][C@@H:11]1[C@@H:50]([OH:51])[C@@H:49]([CH3:52])[C@H:48]([CH3:53])[O:47][C:45](=[O:46])[CH2:44][C@H:43]([OH:54])[CH2:42][C@H:41]([OH:55])[CH2:40][CH2:39][C@@H:38]([OH:56])[C@H:37]([OH:57])[CH2:36][C@H:35]([OH:58])[CH2:34][C@@:32]2([OH:59])[O:33][C@H:28]([C@H:29]([C:61]([OH:63])=[O:62])[C@@H:30]([OH:60])[CH2:31]2)[CH2:27][C@@H:26]([O:64][C@@H:65]2[O:70][C@H:69]([CH3:71])[C@@H:68]([OH:72])[C@H:67]([NH2:73])[C@@H:66]2[OH:74])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=[CH:12]1.C(N(CC)C(C)C)(C)C.C1(C)C=CC(S(OC)(=O)=O)=CC=1>CN(C=O)C>[CH3:10][C@@H:11]1[C@@H:50]([OH:51])[C@@H:49]([CH3:52])[C@H:48]([CH3:53])[O:47][C:45](=[O:46])[CH2:44][C@H:43]([OH:54])[CH2:42][C@H:41]([OH:55])[CH2:40][CH2:39][C@@H:38]([OH:56])[C@H:37]([OH:57])[CH2:36][C@H:35]([OH:58])[CH2:34][C@@:32]2([OH:59])[O:33][C@H:28]([C@H:29]([C:61]([O:63][CH3:2])=[O:62])[C@@H:30]([OH:60])[CH2:31]2)[CH2:27][C@@H:26]([O:64][C@@H:65]2[O:70][C@H:69]([CH3:71])[C@@H:68]([OH:72])[C@H:67]([NH2:73])[C@@H:66]2[OH:74])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=[CH:12]1
Reactant: C[C@@H]1[C@H](O)[C@@H](C)C=CC=CC=CC=CC=CC=CC=C[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N)[C@@H]2O)C[C@@H]2O[C@](O)(C[C@@H](O)C[C@@H](O)[C@H](O)CC[C@@H](O)C[C@@H](O)CC(=O)O[C@H]1C)C[C@H](O)[C@H]2C(=O)O
Reactant: O=Cc1ccc(Cl)cc1
Agent: COC(=O)[C@H]1[C@@H]2C[C@@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@H](N)[C@@H]3O)/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@@H]1O)O2
Agent: COS(=O)(=O)c1ccc(C)cc1
Agent: C[C@@H]1[C@H](O)[C@@H](C)/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N)[C@@H]2O)C[C@@H]2O[C@](O)(C[C@@H](O)C[C@@H](O)[C@H](O)CC[C@@H](O)C[C@@H](O)CC(=O)O[C@H]1C)C[C@H](O)[C@H]2C(=O)O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)[C@H]1[C@@H]2C[C@@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@H](N)[C@@H]3O)C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@@H]1O)O2
Reaction time: 0.5 h

Procedure:
To 1.5 mL of anhydrous DMF in a 3 mL flask was added p-chlorobenzaldehyde (0.0663 g, 4.72×E-4 moles). While purging the flask with nitrogen, Amphotericin B (0.1511 g, 1.51×E-4 moles) is slowly sifted into the vigorously stirred solution over 3 to 4 minutes. All the solid dissolved within 15 minutes and stirring was continued for an additional 30 minutes. At this point all the Amphotericin B was converted to the soluble N-p-chlorobenzylidine derivative. To the clear yellow solution was added N,N-diisopropylethylamine (0.079 mL, 4.53×E-4 moles) followed by methyl p-toluenesulfonate (0.0843 g, 4.53×E-4 moles). The reaction mixture was allowed to stir for 22 hours at ambient temperature and a small aliquot of the reaction mixture was removed and analyzed by reverse phase HPLC. The analysis indicated no unreacted Amphotericin B was present in the reaction mixture. The major component of the product mixture was Amphotericin B methyl ester. The mixture was added to 15 mL of methyl tert.-butyl ether and a yellow solid precipitated. The solid was separated by centrifugation and washed once with 10 mL of methyl tert.-butyl ether. Drying under high vacuum afforded 0.184 g of p-chlorobenzylidine Amphotericin B methyl ester.