Methyl iodide → HCID 68673141, compound

HRID 2264174Notes

Reaction equation

HRID 2264174 reaction equation
[H-].[Na+].I[CH3:4].[OH:5][CH:6]1[C:12]2[CH:13]=[C:14]([CH2:17][N:18]([CH2:34][CH:35]([CH3:37])[CH3:36])[C:19]([CH:21]3[O:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]3)=[O:20])[CH:15]=[CH:16][C:11]=2[CH2:10][CH2:9][CH2:8][CH2:7]1>O1CCCC1.C(=O)(O)[O-].[Na+]>[CH2:34]([N:18]([CH2:17][C:14]1[CH:15]=[CH:16][C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][CH:6]([O:5][CH3:4])[C:12]=2[CH:13]=1)[C:19]([CH:21]1[O:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[CH2:22]1)=[O:20])[CH:35]([CH3:37])[CH3:36]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68674598HCID 68674598, compound

Product 1

HCID 68673141HCID 68673141, compoundYield 110.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a stirred mixture of 25 mg (0.62 mmol, 1.2 equiv) of 60% sodium hydride/mineral oil dispersion and 0.047 mL (0.75 mmol, 1.5 equiv) of iodomethane in 1 mL of anhydrous tetrahydrofuran under nitrogen was added a solution of 230 mg (0.50 mmol) of (±)-tert-butyl 2-{[[(9-hydroxy-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)methyl](isobutyl)amino]-carbonyl}morpholine-4-carboxylate in 1 mL of anhydrous tetrahydrofuran over five minutes. The mixture was stirred at ambient temperature in a sealed flask for three days. The mixture was diluted with 2 mL of saturated sodium bicarbonate solution and extracted with 2×10 mL of ethyl acetate. The extract was washed with 3 mL each of water and brine, dried over sodium sulfate, filtered, and concentrated to give 263 mg of a gum. Purification by flash chromatography (10-50% ethyl acetate in hexanes) gave 171 mg (72%) of product as a solid white foam. MS (m+1)=475.4; H NMR (400 MHz, CDCl3) 7.06 (m, 2H), 6.96 (m, 1H), 4.7 (m, 1H), 4.50 (d, 1H, J 16 Hz), 4.28 (m, 1H), 4.18-4.02 (m, 2H), 3.97-3.80 (m, 2H), 3.50 (m, 1H), 3.31 (d, 3H, J 10 Hz), 3.22 (m, 2H), 2.99 (m, 3H), 2.65 (m, 1H), 2.01 (m, 2H), 1.86 (m, 2H), 1.75 (m, 1H), 1.60 (m, 2H), 1.45 (d, 9H, J 14 Hz), 0.89 (m, 6H).

Workup

  1. extractionextracted with 2×10 mL of ethyl acetate
  2. washThe extract was washed with 3 mL each of water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8fb43b02d9024133ab73f437906e59a6
Source dataset
uspto-grants-2010_12
Patent number
US07855201B2

Reaction notes

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