tetradecanoic acid (3R,6S)-6-{(R)-2-[(4R,5R,6R)-6-((E)-3,3-dimethyl-but-1-enyl)-5-hydroxy-2,2-dimethyl-[1,3]dioxan-4-yl]-2-methoxy-acetylamino}-7-oxo-1-pyridin-3-ylmethyl-azepan-3-yl ester → tetradecanoic acid (3R,6S)-7-oxo-1-pyridin-3-ylmethyl-6-((2R,3R,4S,5R)-(E)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-non-6-enoylamino)-azepan-3-yl ester

HRID 2224024Notes

Reaction equation

HRID 2224024 reaction equation
[CH3:1][C:2]([CH3:52])([CH3:51])/[CH:3]=[CH:4]/[C@H:5]1[O:10]C(C)(C)[O:8][C@@H:7]([C@@H:13]([O:48][CH3:49])[C:14]([NH:16][C@@H:17]2[C:23](=[O:24])[N:22]([CH2:25][C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)[CH2:21][C@H:20]([O:32][C:33](=[O:47])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[CH2:19][CH2:18]2)=[O:15])[C@@H:6]1[OH:50]>C(O)(C(F)(F)F)=O.C1COCC1.O>[O:24]=[C:23]1[N:22]([CH2:25][C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[CH2:21][C@H:20]([O:32][C:33](=[O:47])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[CH2:19][CH2:18][C@@H:17]1[NH:16][C:14](=[O:15])[C@H:13]([O:48][CH3:49])[C@H:7]([OH:8])[C@@H:6]([OH:50])[C@H:5]([OH:10])/[CH:4]=[CH:3]/[C:2]([CH3:1])([CH3:51])[CH3:52]

Participants

3

Reactant 1

HCID 86609576tetradecanoic acid (3R,6S)-6-{(R)-2-[(4R,5R,6R)-6-((E)-3,3-dimethyl-but-1-enyl)-5-hydroxy-2,2-dimethyl-[1,3]dioxan-4-yl]-2-methoxy-acetylamino}-7-oxo-1-pyridin-3-ylmethyl-azepan-3-yl ester

Product 1

HCID 59716389tetradecanoic acid (3R,6S)-7-oxo-1-pyridin-3-ylmethyl-6-((2R,3R,4S,5R)-(E)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-non-6-enoylamino)-azepan-3-yl esterYield 70.7%

Reagents, catalysts & solvents 1

HCID 22185937THF TFA waterSolvent

Procedure

To a solution of TFA/THF/H2O (3/3/2) (30 mL) at 0° C. is added tetradecanoic acid (3R,6S)-6-{(R)-2-[(4R,5R,6R)-6-((E)-3,3-dimethyl-but-1-enyl)-5-hydroxy-2,2-dimethyl-[1,3]dioxan-4-yl]-2-methoxy-acetylamino}-7-oxo-1-pyridin-3-ylmethyl-azepan-3-yl ester (0.3 g, 0.42 mmol). After 30 min the reaction is evaporated under high vacuum, toluene is added (20 mL) and evaporated under high vacuum to remove remaining TFA. The residue is dissolved in CH2Cl2 at 0° C. and neutralized by adding NH4OH dropwise. The solution is concentrated and chromatographed on silica (98% CH2Cl2/2% CH3OH) to give 0.2 g (70.7%) of tetradecanoic acid (3R,6S)-7-oxo-1-pyridin-3-ylmethyl-6-((2R,3R,4S,5R)-(E)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-non-6-enoylamino)-azepan-3-yl ester as a with solid. 1H NMR 300 MHz δ 8.62 (s, 2H), 8.17 (d, 1H), 7.67 (d, 1H), 7.33 (m, 1H), 5.83 (d, 1H), 5.42(dd, 1H), 4.69 (m, 1H), 4.54 (m, 1H), 4.33 (d, 1H), 4.32 (t, 1H), 3.83 (dd, 2H), 3.67 (d, 1H), 3.25 (s, 3H), 3.17 (m, 1H), 2.94 (d, 1H), 2.29 (t, 2H), 2.13 (m, 2H), 2.00 (m, 1H), 1.60 (m, 3H), 1.29 (m, 24H), 1.04 (s, 9H), 0.89 (t, 3H); MS (ESI) 690.3 (M+H)+.

Workup

  1. customAfter 30 min the reaction is evaporated under high vacuum, toluene
  2. additionis added (20 mL)
  3. customevaporated under high vacuum
  4. customto remove
  5. dissolutionThe residue is dissolved in CH2Cl2 at 0° C.
  6. additionby adding NH4OH dropwise
  7. concentrationThe solution is concentrated
  8. customchromatographed on silica (98% CH2Cl2/2% CH3OH)

Sources & evidence

ORD record
ord-96b5781e245141c2a85193b49e927705
Source dataset
uspto-grants-2008_05
Patent number
US07378410B2

Reaction notes

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