Methyl iodide → (4aR,5R,8S,8aR)-5-[(4-fluorophenyl)amino]-8-(methoxymethyl)hexahydro-2H-chromen-4a(5H)-ol

HRID 73646Notes

Reaction equation

HRID 73646 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C@@H:9]2[CH2:18][CH2:17][C@@H:16]([CH2:19][OH:20])[C@@H:15]3[C@:10]2([OH:21])[CH2:11][CH2:12][CH2:13][O:14]3)=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:25].[NH4+].[Cl-]>C1COCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C@@H:9]2[CH2:18][CH2:17][C@@H:16]([CH2:19][O:20][CH3:25])[C@@H:15]3[C@@:10]2([OH:21])[CH2:11][CH2:12][CH2:13][O:14]3)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 68154178(4aS,5R,8S,8aR)-5-[(4-fluorophenyl)amino]-8-(hydroxymethyl)hexahydro-2H-chromen-4a(5H)-ol

Product 1

HCID 68154263(4aR,5R,8S,8aR)-5-[(4-fluorophenyl)amino]-8-(methoxymethyl)hexahydro-2H-chromen-4a(5H)-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Dissolved 95 mg (4aS,5R,8S,8aR)-5-[(4-fluorophenyl)amino]-8-(hydroxymethyl)hexahydro-2H-chromen-4a(5H)-ol in 2.1 mL THF then added 39 mg NaH. The reaction was stirred for 1.5 hours at RT, then diluted with an additional 1 mL of THF before adding 50 uL iodomethane. The reaction was stirred overnight at RT, then added to sat. NH4Cl. The mixture was diluted with water and extracted with CH2Cl2. The crude extract was dried over Na2SO4 then filtered, concentrated, then purified on silica gel to provide the title compound. 3H NMR (500 MHz, CDCl3) δ=1.34-1.40 (m, 2H), 1.54-1.62 (m, 2H), 1.72-1.77 (m, 1H), 1.78-1.87 (m, 1H), 2.10-2.16 (m, 1H), 2.22-2.30 (m, 1H), 2.32-2.42 (m, 1H), 3.29 (dd, J1=9.3 Hz, J2=6.6 Hz, 1H), 3.31-3.33 (m, 1H), 3.44-3.50 (m, 2H), 3.53 (bd, J=11.2 Hz), 4.09 (dd, Jz=11.6 Hz, J2=6.5 Hz, 1H), 4.58 (d, J=11.2 Hz) ppm. HRMS (ES) m/z calc'd: 310.1813. found 310.1811.

Workup

  1. stirringThe reaction was stirred overnight at RT
  2. extractionextracted with CH2Cl2
  3. extractionThe crude extract
  4. dry with materialwas dried over Na2SO4
  5. filtrationthen filtered
  6. concentrationconcentrated
  7. custompurified on silica gel

Sources & evidence

ORD record
ord-1087bc00681c4cc1a7cc047e8c8389fb
Source dataset
uspto-grants-2014_09
Patent number
US08829196B2

Reaction notes

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