Methyl iodide → HCID 71152529, compound

HRID 1497281Notes

Reaction equation

HRID 1497281 reaction equation
[NH2:1][C@@H:2]1[C@@H:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C@H:6]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:5]([CH2:24][F:25])[CH2:4][C@@H:3]1[OH:26].C(S[N:30]=[C:31]=O)C.CI.[CH2:35]1[CH2:39]OCC1>CC(C)=O.C([O-])(O)=O.[Na+]>[CH2:9]([O:8][C@@H:7]1[C@H:2]2[N:1]=[C:31]([NH:30][CH2:39][CH3:35])[O:26][C@H:3]2[CH2:4][C@H:5]([CH2:24][F:25])[C@H:6]1[O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8028Tetrahydrofuran2×HCID 21933416HCID 21933416, compoundHCID 117857041HCID 117857041, compound

Product 1

HCID 71152529HCID 71152529, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (1S,2S,3R,4R,5S)-2-amino-3,4-bis(benzyloxy)-5-(fluoromethyl)cyclohexanol (182 mg, 0.507 mmol) in THF (4 mL) at room temperature was added a solution of ethylthioisocyanate (55 mg, 0.63 mmol) in THF (1 mL). The mixture was stirred at room temperature for 18 h. The solvent was evaporated to give a colorless syrup. This was dissolved in acetone (3 mL) and MeI (144 mg, 1.01 mmol) was added. The mixture was stirred at room temperature for 6 h. The reaction was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with DCM (3×10 mL). The extracts were dried with Na2SO4 and the solvents were evaporated to give (3aS,4R,5R,6S,7aS)-4,5-bis(benzyloxy)-N-ethyl-6-(fluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazol-2-amine as a white solid (209 mg, 100%) which was pure enough for next reaction. MS m/z 413.2 (M+1, 100%); 1H NMR (400 MHz, CDCl3) δ 7.27-7.39 (m, 10H), 4.86 (d, J=11.7 Hz, 1H), 4.80 (d, J=11.2 Hz, 1H), 4.70 (d, J=11.6 Hz, 1H), 4.69-4.73 (m, 1H), 4.64 (dd, J=9.0 Hz, 4.5 Hz, 0.5H), 4.45-4.53 (m, 1H), 4.48 (d, J=11.2 Hz, 1H), 4.35 (dd, J=8.9 Hz, 2.9 Hz, 0.5H), 4.09 (dd, J=8.0 Hz, 5.2 Hz, 1H), 3.67 (t, J=5.6 Hz, 1H), 3.46 (dd, J=9.3 Hz, 6.1 Hz, 1H), 3.16-3.29 (m, 2H), 2.12 (dt, J=14.6 Hz, 2.9 Hz, 1H), 1.91-2.06 (m, 1H), 1.79-1.87 (m, 1H), 1.15 (t, J=7.2 Hz, 3H).

Workup

  1. customThe solvent was evaporated
  2. customto give a colorless syrup
  3. stirringThe mixture was stirred at room temperature for 6 h
  4. extractionextracted with DCM (3×10 mL)
  5. dry with materialThe extracts were dried with Na2SO4
  6. customthe solvents were evaporated

Sources & evidence

ORD record
ord-b68c066a64c44fafbfdc7b20f44e4210
Source dataset
uspto-grants-2015_12
Patent number
US09199949B2

Reaction notes

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