Benzyl chloromethyl ether → HCID 71116129, compound

HRID 715512Notes

Reaction equation

HRID 715512 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][N:10]2[CH2:14][C:13]3([CH2:19][CH2:18][CH2:17][CH:16]([C:20]([O:22][CH3:23])=[O:21])[CH2:15]3)[O:12][C:11]2=[O:24])=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl[CH2:36][O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][N:10]2[CH2:14][C:13]3([CH2:19][CH2:18][CH2:17][C:16]([CH2:36][O:37][CH2:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)([C:20]([O:22][CH3:23])=[O:21])[CH2:15]3)[O:12][C:11]2=[O:24])=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 137983Benzyl chloromethyl etherHCID 2724254Sodium bis(trimethylsilyl)amideHCID 71116119HCID 71116119, compound

Product 1

HCID 71116129HCID 71116129, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of methyl 3-{[4-(methyloxy)phenyl]methyl}-2-oxo-1-oxa-3-azaspiro[4.5]decane-7-carboxylate (5.05 g, 15.15 mmol) in THF (38.7 mL) under nitrogen at −78° C. was added sodium bis(trimethylsilyl)amide, (1M in THF, 45.4 mL, 45.4 mmol) over 30 minutes. The reaction mixture was stirred at −78° C. for 1 h. Benzyl chloromethyl ether (7.12 g, 45.4 mmol) was then added. After 1 h, the reaction was quenched slowly with water (5 mL). Saturated aq NaCl (100 mL) was then added and the mixture was extracted with EtOAc (2×125 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The compound was then loaded onto florisil and purified using silica gel chromatography CISCO): 10-25% ethyl acetate/hexanes (30 min), 25% (5 min.), 25-45% (15 min), 45% (5 min), 120 g silica. The product eluted at 45 minutes. Methyl 3-{[4-(methyloxy)phenyl]methyl}-2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]decane-7-carboxylate was obtained as a light yellow oil (4.62 g, 64% yield) and NMR and LCMS were 95% clean for trans product. MS (m/z) 454.0 (M+H+).

Workup

  1. waitAfter 1 h
  2. customthe reaction was quenched slowly with water (5 mL)
  3. additionSaturated aq NaCl (100 mL) was then added
  4. extractionthe mixture was extracted with EtOAc (2×125 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified
  9. custom10-25% ethyl acetate/hexanes (30 min), 25% (5 min.), 25-45% (15 min), 45% (5 min), 120 g silica
  10. washThe product eluted at 45 minutes

Sources & evidence

ORD record
ord-f7c0f37a23234e7d9305c6736a6fc12b
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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