Trifluoroacetic acid → (13E)-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[1-(3-phenyloxiran-2-yl)ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone

HRID 849820Notes

Reaction equation

HRID 849820 reaction equation
[CH3:1][C@@H:2]([CH:12]1[O:31][C:29](=[O:30])[C@H:28]([CH2:32][CH:33]([CH3:35])[CH3:34])[O:27][C:25](=[O:26])[C:24](C)([CH3:36])[CH2:23][NH:22][C:20](=[O:21])[C@@H:19]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[C:41]([Cl:47])[CH:40]=2)[NH:18][C:16](=[O:17])[CH:15]=[CH:14][CH2:13]1)[C@@H:3]1[O:5][C@H:4]1[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C1(P(=S)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C1C=CC=CC=1>[CH3:36][CH:24]1[C:25](=[O:26])[O:27][CH:28]([CH2:32][CH:33]([CH3:34])[CH3:35])[C:29](=[O:30])[O:31][CH:12]([CH:2]([CH:3]2[O:5][CH:4]2[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH3:1])[CH2:13][CH:14]=[CH:15][C:16](=[O:17])[NH:18][CH:19]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[C:41]([Cl:47])[CH:40]=2)[C:20](=[O:21])[NH:22][CH2:23]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 19758Phosphine sulfide, triphenyl-HCID 516892Sodium BicarbonateHCID 76210636186256-68-8

Product 1

HCID 5468287(13E)-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[1-(3-phenyloxiran-2-yl)ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetroneYield 41.4%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To a solution of Cryptophycin 53 (5 mg, 0.007 mmol) in 0.5 mL of dry benzene was added triphenylphosphine sulfide (4 mg, 0.014 mmol) followed by 0.65 μL of trifluoroacetic acid as a solution in dry benzene (100 μl). The solution was allowed to stir at room temperature for 6 h, neutralized with sodium bicarbonate, filtered and evaporated. The residue was partitioned between water and CH2Cl2. The CH2Cl2 -soluble material was purified by reversed-phase HPLC on C18 using 4:1 MeCN/H2O to obtain pure Cryptophycin 61 (1.9 mg, 37%). 1H NMR (300 MHz, CDCl3) unit A 7.24-7.35 (10/11/12/13/14-H; m), 6.73 (3-H; ddd, 15.0/10.2/4.8), 5.67 (2-H; d, 15.0), 5.23 (5-H; bm, W1/2 ≈15 Hz), 3.68 (8-H; d, 5.1), 3.01 (7-H; dd, 8.3/5.1), 2.52 (4-Hb ; bm, W1/2 ≈15 Hz), 2.41 (4-Ha ; ddd, -14.6/11.1/10.8), 1.6-1.8 (6-H; m), 1.15 (6-Me; d, 6.9); unit B 7.18 (5-H; d, 2.1), 7.04 (9-H; dd, 8.4/2.1), 6.84 (8-H; d, 8.4), 5.45 (NH; d, 7.8), 4.75 (2-H; ddd, 7.8/7.2/6.9), 3.88 (OMe; s), 3.08 (3-Hb /3-Ha ; bm, W1/2 ≈15 Hz); unit C 7.17 (NH; m), 3.40 (3-Hb ; dd, -13.6/8.4), 3.13 (3-Ha ; dd, -13.6/3.6), 1.23* (2-Me; s), 1.16* (2-Me'; s); unit D 4.86 (2-H; dd, 9.9/3.6), 1.6-1.8 (3-Hb /4-H, m), 1.43 (3-Ha ; bm, W1/2 ≈15 Hz), 0.92.dagger. (4-Me; d, 6.6), 0.88.dagger. (5-H3 ; d, 6.6).

Workup

  1. filtrationfiltered
  2. customevaporated
  3. customThe residue was partitioned between water and CH2Cl2
  4. customThe CH2Cl2 -soluble material was purified by reversed-phase HPLC on C18 using 4:1 MeCN/H2O

Sources & evidence

ORD record
ord-adb4612f2d7449aa94866eb48582ec45
Source dataset
uspto-grants-2000_01
Patent number
US06013626

Reaction notes

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