Methyl iodide → HCID 178490973, compound

HRID 2273028Notes

Reaction equation

HRID 2273028 reaction equation
[NH2:1][CH:2]1[CH:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:5]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:4][CH:3]1[OH:33].[CH3:34][O:35][C:36]1[CH:45]=[CH:44][C:39]([CH2:40][N:41]=[C:42]=S)=[CH:38][CH:37]=1.CI.C([O-])(O)=O.[Na+]>C1COCC1>[CH2:9]([O:8][CH:7]1[CH:2]2[N:1]=[C:42]([NH:41][CH2:40][C:39]3[CH:44]=[CH:45][C:36]([O:35][CH3:34])=[CH:37][CH:38]=3)[O:33][CH:3]2[CH2:4][CH:5]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]1[O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 123197Benzene, 1-(isothiocyanatomethyl)-4-methoxy-HCID 516892Sodium BicarbonateHCID 67480625HCID 67480625, compound

Product 1

HCID 178490973HCID 178490973, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of Intermediate B (180 mg, 0.403 mmol) in dry THF (3 mL) was added a solution of 4-methoxybenzyl isothiocyanate (94%, 96 mg, 0.50 mmol) in dry THF (2 mL). The mixture was stirred at room temperature for 28 h. Solvents were evaporated under reduced pressure. The residue was dissolved in acetone (3 mL). MeI (114 mg, 0.805 mmol) was added. The mixture was stirred at room temperature for 2 h. Satd. aqueous NaHCO3 (2 mL) was added and stirred at room temperature for 10 min. The mixture was further diluted with satd. aqueous NaHCO3 (20 mL), extracted with EtOAc (2×15 mL). The combined extracts were washed with brine and dried over Na2SO4. Solvents were evaporated under reduced pressure. The crude product was purified by silica gel column chromatography, eluted with 96:3:1 EtOAc-MeOH—NH4OH (28% aqueous) to give rac-(3aS,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-N-(4-methoxybenzyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazol-2-amine (159 mg, 67%) as a syrup. 1H NMR (400 MHz, CDCl3) δ 7.37-7.25 (m, 15H), 7.21 (d, J=8.6 Hz, 2H), 6.81 (d, J=8.6 Hz, 2H), 4.80 (m, 1H), 4.79 (d, J=11.3 Hz, 1H), 4.77 (d, J=10.1 Hz, 1H), 4.66 (d, J=11.5 Hz, 1H), 4.45 (s, 2H), 4.44 (d, J=11.2 Hz, 1H), 4.35 (d, J=13.9 Hz, 1H), 4.25 (d, J=13.9 Hz, 1H), 4.07 (dd, J=7.9, 5.4 Hz, 1H), 3.76 (s, 3H), 3.64 (t, J=5.8 Hz, 1H), 3.56 (dd, J=10.2, 5.0 Hz, 1H), 3.51 (dd, J=8.2, 6.5 Hz, 1H), 3.47 (dd, J=9.1, 3.8 Hz, 1H), 2.17 (dt, J=14.7, 3.4 Hz, 1H), 2.06-1.97 (m, 1H), 1.88 (ddd, J=15.2, 12.1, 3.6 Hz, 1H).

Workup

  1. customSolvents were evaporated under reduced pressure
  2. dissolutionThe residue was dissolved in acetone (3 mL)
  3. stirringThe mixture was stirred at room temperature for 2 h
  4. stirringstirred at room temperature for 10 min
  5. additionThe mixture was further diluted with satd
  6. extractionaqueous NaHCO3 (20 mL), extracted with EtOAc (2×15 mL)
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. customSolvents were evaporated under reduced pressure
  10. customThe crude product was purified by silica gel column chromatography
  11. washeluted with 96:3:1 EtOAc-MeOH—NH4OH (28% aqueous)

Sources & evidence

ORD record
ord-7ff9212a7b154225b9cfed517a951d5a
Source dataset
uspto-grants-2015_09
Patent number
US09120781B2

Reaction notes

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