Acetaldehyde → Tert-butyl 8-ethyl-10-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72867Notes

Reaction equation

HRID 72867 reaction equation
[C:1]1([CH:7]2[CH2:24][NH:23][CH2:22][C:9]3([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]3)[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:25](=O)[CH3:26].C([BH3-])#N.[Na+]>CO>[CH2:25]([N:23]1[CH2:24][CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][C:9]2([CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[CH2:13][CH2:14]2)[CH2:22]1)[CH3:26]

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 68291603Tert-butyl 2-phenyl-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 70872556Tert-butyl 8-ethyl-10-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of tert-butyl 8-phenyl-7-oxa-3,10-diazaspiro[5.5]undecane-3-carboxylate (735 mg, 2.21 mmol) in methanol (10 mL) was added acetaldehyde (107 mg, 136 μL, 2.43 mmol), then sodium cyanoborohydride (195 mg, 1.5 mL, 3.10 mmol) and the reaction mixture was stirred for 2 hours. The reaction mixture was concentrated in vacuo, diluted with DCM (50 mL), washed with 1:1 aq. sat. NaHCO3/25% NaOH (10 mL), and the aqueous layer was extracted with DCM (2×25 mL). The combined organics were dried (MgSO4), concentrated in vacuo and purified by silica gel column chromatography using (0-75% EtOAc/DCM) as eluent to give tert-butyl 8-ethyl-10-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (540 mg, 68%) as a viscous yellow oil. ESI-MS m/z calc. 360.5. Found 361.7 (M+1)+; Retention time: 1.15 minutes (3 min run).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with DCM (50 mL)
  3. washwashed with 1:1 aq. sat. NaHCO3/25% NaOH (10 mL)
  4. extractionthe aqueous layer was extracted with DCM (2×25 mL)
  5. dry with materialThe combined organics were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-788ae555ad4742a48eef88a9fe767a8d
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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