Methyl iodide → HCID 86755236, compound

HRID 1637048Notes

Reaction equation

HRID 1637048 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[CH2:13]([N:16]([C@@H:32]([CH3:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C@@H:17]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:14]=[CH2:15].CI>O1CCCC1>[CH3:1][C@@H:18]([C@@H:17]([N:16]([C@@H:32]([CH3:39])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH2:13][CH:14]=[CH2:15])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 86755237HCID 86755237, compoundHCID 178418339Butyllithium

Product 1

HCID 86755236HCID 86755236, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of diisopropylamine (0.691 ml, 4.93 mmol) in anhydrous tetrahydrofuran (10 ml) was cooled to -78° C. prior to the dropwise addition of 1.6M butyllithium (2.57 ml, 4.11 mmol) via a syringe. The solution was warmed to 0° C. and then immediately recooled to -78° C., whereupon a solution of compound (8) from Example 2 (600 mg, 1.64 mmol) in tetrahydrofuran (10 ml) was added dropwise via a cannula. Stirring was continued for 1 hour at -78° C. followed by the rapid injection of methyl iodide (0.512 ml, 8.22 mmol). The reaction mixture was allowed to warm slowly to room temperature overnight (16 hours) after which the solvent was evaporated. The residue was partitioned between ethyl acetate (50 ml) and brine (25 ml) and the organic layer was dried (magnesium sulphate), filtered and evaporated to yield a yellow oil. This was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:49)] affording the title compound (51) in 94% diastereoisomeric excess (Rf 0.25) as a colourless oil (406 mg, 65%). δH (300 MHz, CDCl3) 7.41-7.17 (10H, m, Ph), 5.93-5.79 (1H, m, NCH2CH=CH2), 5.11 (1H, app. dd, J=17.3 and 1.3, trans CH=CH2), 5.08 (1H, app. dd, J=10.1 and 1.1, cis CH=CH2), 4.18 (1H, d, J=11.4, PhCHCH3), 3.29 (1H, app. ddt, J=14.7, 5.0 and 1.9, NCH2), 3.19 (1H, dq, J=11.4 and 6.9, CHCHCH3), 3.10 (1H, dd, J=14.7 and 8.0, NCH2), 1.50 (9H, s, (CH3)3C), 0.94 (3H, d, J=6.7, PhCHCH3), 0.90 (3H, d, J=6.9, CHCHCH3).

Workup

  1. additionwas added dropwise via a cannula
  2. temperatureto warm slowly to room temperature overnight (16 hours) after which the solvent
  3. customwas evaporated
  4. customThe residue was partitioned between ethyl acetate (50 ml) and brine (25 ml)
  5. dry with materialthe organic layer was dried (magnesium sulphate)
  6. filtrationfiltered
  7. customevaporated
  8. customto yield a yellow oil
  9. customThis was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:49)]

Sources & evidence

ORD record
ord-0ade37a7c11043f183000a20ed7b98c1
Source dataset
uspto-grants-2000_03
Patent number
US06037498

Reaction notes

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