4-Methylmorpholine → HCID 58294849, compound

HRID 422180Notes

Reaction equation

HRID 422180 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](O)=[O:27])[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.Cl.[CH3:61][O:62][C:63](=[O:66])[CH2:64][NH2:65]>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]([NH:65][CH2:64][C:63]([O:62][CH3:61])=[O:66])=[O:27])[CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 122755Glycine methyl ester hydrochlorideHCID 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 58294849HCID 58294849, compoundYield 54%

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) (0.20 g, 0.49 mmol), HATU (0.37 g, 0.98 mmol), N-methyl morpholine (0.2 mL, 3 mmol) and glycine methyl ester hydrochloride (0.09 g, 2 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 (CH2Cl2/MeOH, 10:1) to give methyl 2-{[(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-trien-3-yl]formamido}acetate (90) (0.05 g, 54%) as a cream solid. 1H NMR (CDCl3): δ 7.37 (s, 1H), 7.21 (d, 1H), 6.89 (d, 1H), 6.70 (m, 1H), 4.19 (m, 2H), 3.81 (s, 3H), 3.40 (m, 2H), 2.62 (m, 1H), 2.16 (m, 1H), 1.76-1.34 (m, 10H), 1.20-1.00 (m, 2H), 0.98-0.92 (m, 4H), 0.89 (s, 3H), 0.82 (s, 3H). MS m/z 476 (C25H35NO6S−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 (CH2Cl2/MeOH, 10:1)

Sources & evidence

ORD record
ord-f55e9efebd7f40adb72157685763004d
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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