Ethyl Acetate → HCID 178481515, compound

HRID 1045987Notes

Reaction equation

HRID 1045987 reaction equation
CC(C)([S@]([NH:6][C@@:7]([CH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)([CH3:13])[CH2:8][C:9]([O:11]C)=O)=O)C.[C:21]([NH:25][C:26]([NH:28]C(NC)=S)=O)(C)(C)C.C(N(CC)[CH:37]([CH3:39])[CH3:38])(C)C.Cl.[CH3:43]N(C)CCCN=C=NCC.CC[O:56][C:57](C)=[O:58]>O.Cl.CO.C(Cl)Cl>[CH3:21][N:25]1[C:9](=[O:11])[CH2:8][C@@:7]([CH3:13])([CH:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)[NH:6][C:26]1=[N:28][C:57](=[O:58])[O:56][C:37]([CH3:38])([CH3:39])[CH3:43]

Participants

10

Reactant 5

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57475693HCID 57475693, compoundHCID 68153908HCID 68153908, compound

Product 1

HCID 178481515HCID 178481515, compoundYield 85%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (S)-methyl 3-((R)-1,1-dimethylethylsulfinamido)-3-(tetrahydro-2H-pyran-4-yl)butanoate 5 (6.5 g, 21 mmol), DCM (70 mL), and MeOH (35 mL) was added hydrogen chloride solution (4.0 M in 1,4-dioxane, 79.8 mL). The resulting mixture was stirred at RT for 2 h. At that time, the reaction was concentrated and then diluted with toluene (100 mL) and re-concentrated. This material was dissolved in DMF (100 mL) and N-tert-butylcarbamoyl-N′-methylthiourea (5.06 g, 26.6 mmol), N,N-diisopropylethylamine (16.7 mL, 95.8 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.12 g, 31.9 mmol) were added. The mixture was immersed in a 45° C. oil bath and allowed to stir overnight. After 16 h, the reaction was diluted with water (200 mL), 3N HCl (50 mL) and EtOAc and stirred vigorously for 10 min. The phases were separated and the aqueous layer was extracted 2× with EtOAc. The organic portions were combined, washed with sat. aq. NaHCO3 and brine, dried over MgSO4, filtered and concentrated. This crude sample was subjected to column chromatography (ISCO, 330 g silica, 100 ml/min, 0% to 100% EtOAc/hexanes) to give (S)-tert-butyl 1,4-dimethyl-6-oxo-4-(tetrahydro-2H-pyran-4-yl)tetrahydropyrimidin-2(1H)-ylidenecarbamate 6 (5.9 g, 85%). 1H NMR (400 MHz, CDCl3) for 6: δ=9.98 (s, 1 H), 4.03 (m, 2 H), 3.34 (m, 2 H), 3.27 (s, 3 H), 2.62 (ABq, JAB=16.4 Hz, ΔνAB=66.8 Hz, 2 H), 1.66 (m, 1 H), 1.57 (m, 2 H), 1.49 (s, 9 H), 1.43 (m, 3 H), 1.25 (s, 3 H). LCMS for 6 (conditions D): tR=1.86 min, m/e=326.3 (M+H), 270.2 (M−t−Bu+H, base).

Workup

  1. concentrationAt that time, the reaction was concentrated
  2. additiondiluted with toluene (100 mL)
  3. concentrationre-concentrated
  4. dissolutionThis material was dissolved in DMF (100 mL)
  5. customwas immersed in a 45° C.
  6. stirringto stir overnight
  7. waitAfter 16 h
  8. stirringstirred vigorously for 10 min
  9. customThe phases were separated
  10. extractionthe aqueous layer was extracted 2× with EtOAc
  11. washwashed with sat. aq. NaHCO3 and brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-b2904500e42341bba2565a383f1efac1
Source dataset
uspto-grants-2013_10
Patent number
US08569310B2

Reaction notes

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