Allylamine → Tert-butyl 2-(allylcarbamoyl)-4-(2,2-difluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 72877Notes

Reaction equation

HRID 72877 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][C:11]2([O:16][CH:15]([C:17](O)=[O:18])[CH2:14][N:13]([CH2:20][CH:21]([F:23])[F:22])[CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:26]([NH2:29])[CH:27]=[CH2:28].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.C(N(CC)CC)C>CC1CCCO1>[CH2:26]([NH:29][C:17]([CH:15]1[CH2:14][N:13]([CH2:20][CH:21]([F:23])[F:22])[CH2:12][C:11]2([CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:25][CH2:24]2)[O:16]1)=[O:18])[CH:27]=[CH2:28]

Participants

6

Reactant 4

HCID 7853AllylamineHCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 86672461HCID 86672461, compound

Product 1

HCID 86672460Tert-butyl 2-(allylcarbamoyl)-4-(2,2-difluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylateYield 83.2%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To 9-(tert-butoxycarbonyl)-4-(2,2-difluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2-carboxylic acid (520 mg, 1.43 mmol), prop-2-en-1-amine (118 μL, 1.57 mmol) and T3P (2.12 mL of 50% w/w, 3.59 mmol) in 2-methyltetrahydrofuran (4 mL) was added triethylamine (597 μL, 4.28 mmol) at room temperature and the reaction mixture was stirred for 2 hours. The reaction mixture was then quenched with saturated NaHCO3 solution (3 mL) and stirred for an additional 10 minutes, then diluted with EtOAc and the layers were separated. The aqueous layer was extracted once more with EtOAc, and the combined organics were dried over Na2SO4, filtered and concentrated in vacuo to an oil. The residue was purified by silica gel column chromatography using 0-50% EtOAc in hexanes to yield tert-butyl 2-(allylcarbamoyl)-4-(2,2-difluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (480 mg, 83%). ESI-MS m/z calc. 403.2. Found 404.5 (M+1)+; Retention time: 1.78 minutes (3 min run).

Workup

  1. customThe reaction mixture was then quenched with saturated NaHCO3 solution (3 mL)
  2. stirringstirred for an additional 10 minutes
  3. additiondiluted with EtOAc
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted once more with EtOAc
  6. dry with materialthe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to an oil
  9. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6e89c0ec58d04c13b04eada5ac312a2b
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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