4-Methylmorpholine → (1R,10R,11S,16S)-3-hydroxy-N-methoxy-1,11,15,15-tetramethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxamide

HRID 422186Notes

Reaction equation

HRID 422186 reaction equation
C[O:2][C:3]1[CH:20]=[C:19]([C:21]([OH:23])=O)[CH:18]=[C:17]2[C:4]=1[C@H:5]1[C@H:14]([CH2:15][S:16]2(=[O:25])=[O:24])[C@:13]2([CH3:26])[C@H:8]([C:9]([CH3:28])([CH3:27])[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]1.CN([C:32]([O:36][N:37]1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:53]N1CCOCC1.Cl.CON>C1COCC1.CN(C=O)C>[OH:2][C:3]1[CH:20]=[C:19]([C:21]([NH:37][O:36][CH3:32])=[O:23])[CH:18]=[C:17]2[C:4]=1[C@@:5]1([CH3:53])[C@H:14]([CH2:15][S:16]2(=[O:25])=[O:24])[C@:13]2([CH3:26])[C@H:8]([C:9]([CH3:27])([CH3:28])[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86654189(1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid

Product 1

HCID 53240947(1R,10R,11S,16S)-3-hydroxy-N-methoxy-1,11,15,15-tetramethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxamideYield 28.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid (61) (0.20 g, 0.49 mmol), HATU (0.37 g, 0.98 mmol), N-methylmorpholine (0.20 mL, 3.0 mmol) and methoxyamine hydrochloride (0.12 g, 1.5 mmol) in THF (10 mL) and DMF (2.0 mL) was stirred at room temperature for 18 h. The THF was evaporated under reduced pressure, the residue was quenched with water and the resulting solid was collected by filtration. The crude product was purified by flash column chromatography on silica gel (Hexanes/EtOAc, 1:2) to give (1R,10R,11S,16S)-3-hydroxy-N-methoxy-1,11,15,15-tetramethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxamide (96) (0.06 g, 28%) as a white solid. 1H NMR (CD3OD): δ 7.64 (d, 1H), 7.37 (d, 1H), 3.79 (s, 3H), 3.58 (m, 1H), 3.36 (m, 2H), 2.24 (d, 1H), 1.86-1.16 (m, 12H), 1.09-0.99 (m, 5H), 0.90 (s, 3H), 0.88 (s, 3H). MS m/z 434 (C23H33NO5S−H+).

Workup

  1. customThe THF was evaporated under reduced pressure
  2. customthe residue was quenched with water
  3. filtrationthe resulting solid was collected by filtration
  4. customThe crude product was purified by flash column chromatography on silica gel (Hexanes/EtOAc, 1:2)

Sources & evidence

ORD record
ord-133ebe22c5ec4873b9e4657f57bd8ea2
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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