4-Methylmorpholine → HCID 53240853, compound

HRID 422178Notes

Reaction equation

HRID 422178 reaction equation
[OH:1][C:2]1[CH:19]=[C:18]2[C:5]([C@@:6]3([CH3:25])[C@H:15]([CH2:16][S:17]2(=[O:21])=[O:20])[C@:14]2([CH3:22])[C@H:9]([C:10]([CH3:24])([CH3:23])[CH2:11][CH2:12][CH2:13]2)[CH2:8][CH2:7]3)=[C:4]([C:26]([OH:28])=O)[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C[N:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1.N1CCOCC1>C1COCC1.CN(C=O)C>[OH:1][C:2]1[CH:19]=[C:18]2[C:5]([C@@:6]3([CH3:25])[C@H:15]([CH2:16][S:17]2(=[O:21])=[O:20])[C@:14]2([CH3:22])[C@H:9]([C:10]([CH3:23])([CH3:24])[CH2:11][CH2:12][CH2:13]2)[CH2:8][CH2:7]3)=[C:4]([C:26]([N:54]2[CH2:59][CH2:58][O:57][CH2:56][CH2:55]2)=[O:28])[CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 8083MorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53240650HCID 53240650, compound

Product 1

HCID 53240853HCID 53240853, compoundYield 52.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (1R,10R,11S,16S)-5-hydroxy-1,11,15,15-tetramethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxylic acid (65) (0.06 g, 0.2 mmol), HATU (0.15 g, 0.40 mmol), N-methylmorpholine (0.04 mL, 0.6 mmol) and morpholine (0.1 mL, 1 mmol) in THF (4.0 mL) and DMF (1.0 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, 3:1) to give (1R,10R,11S,16S)-5-hydroxy-1,11,15,15-tetramethyl-3-[(morpholin-4-yl)carbonyl]-8λ6-thiatetracyclo-[8.8.0.02,7.011,16]octadeca-2,4,6-triene-8,8-dione (88) (0.05 g, 45%) as a tan solid. 1H NMR (DMSO-d6): δ 8.49 (s, 1H), 7.14 (s, 1H), 6.75 (s, 1H), 3.72-3.14 (m, 10H), 2.44 (m, 1H), 2.00 (d, 1H), 1.83 (d, 1H), 1.70-1.32 (m, 8H), 1.28-1.22 (m, 1H), 1.12 (m, 1H), 0.96 (m, 1H), 0.89 (s, 3H), 0.86 (m, 3H), 0.82 (m, 1H), 0.79 (s, 3H). MS m/z 476 (C26H37NO6S+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, 3:1)

Sources & evidence

ORD record
ord-fb07f0aefc0848858c9feb224900b318
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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