4-Methylmorpholine → methyl 2-{[(1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-trien-5-yl]formamido}acetate

HRID 422182Notes

Reaction equation

HRID 422182 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.[CH3:29]N(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:2][C:3]1[CH:20]=[C:19]([C:21]([NH:65][CH2:64][C:63]([O:62][CH3:61])=[O:66])=[O:23])[CH:18]=[C:17]2[C:4]=1[C@@:5]1([CH3:29])[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 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 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 58294834methyl 2-{[(1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-trien-5-yl]formamido}acetateYield 42.7%

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 glycine methyl ester hydrochloride (0.18 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 (CH2Cl2/MeOH, 10:1) to give methyl 2-{[(1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-trien-5-yl]formamido}acetate (92) (0.10 g, 42%) as a white solid. 1H NMR (CDCl3): δ 8.16 (s, 1H), 7.81 (d, 1H), 7.71 (d, 1H), 7.18 (m, 1H), 4.24 (m, 2H), 3.32 (m, 3H), 2.30 (d, 1H), 1.76-1.00 (m, 16H), 0.97 (s, 3H), 0.88 (s, 3H), 0.84 (s, 3H). MS m/z 478 (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-3ae4d24f02ed41859229c91272075010
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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