Triethylamine → 4-[4-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-4-oxo-butyl]-5-oxo-[1,4]diazepane-1-carboxylic acid benzyl ester

HRID 2095513Notes

Reaction equation

HRID 2095513 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH2:16][C:15](=[O:18])[N:14]([CH2:19][CH2:20][CH2:21][CH2:22][OH:23])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)N([O])C(C)(C)CCC1.C(OI(C1C=CC=CC=1)OC(=O)C)(=O)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.Cl.[CH2:82]1[C:84]2([CH2:89][CH2:88][NH:87][CH2:86][C@H:85]2[OH:90])[CH2:83]1.C([O-])(O)=O.[Na+]>C(#N)C.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH2:16][C:15](=[O:18])[N:14]([CH2:19][CH2:20][CH2:21][C:22]([N:87]2[CH2:88][CH2:89][C:84]3([CH2:82][CH2:83]3)[C@H:85]([OH:90])[CH2:86]2)=[O:23])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 7

HCID 8471TriethylamineHCID 76724Iodobenzene diacetateHCID 516892Sodium BicarbonateHCID 2724126TempoHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44541812(4S)-6-Azaspiro[2.5]octan-4-ol hydrochloride2×HCID 670748254-(4-Hydroxy-butyl)-5-oxo-[1,4]diazepane-1-carboxylic acid benzyl ester

Product 1

HCID 670743214-[4-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-4-oxo-butyl]-5-oxo-[1,4]diazepane-1-carboxylic acid benzyl esterYield 55%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To an ice cold solution of 0.44 g (1.4 mmol) of 4-(4-hydroxy-butyl)-5-oxo-[1,4]diazepane-1-carboxylic acid benzyl ester in 5 ml of acetonitrile:water (1:1) was added 0.043 g (0.3 mmol) TEMPO and 0.97 g (3.0 mmol) of (diacetoxyiodo)benzene. The mixture was stirred allowed to reach room temperature and was stirred for a further 3 h after which time it was evaporated to dryness. The crude residue was redissolved in 5 ml of DMF, 0.68 g (2 mmol) of HATU and 0.6 ml (4.0 mmol) of triethylamine added followed by addition of 0.25 g (2.0 mmol) of (S)-6-aza-spiro[2.5]octan-4-ol. hydrochloride (intermediate 2). The reaction was stirred for 16 h after which time the mixture was poured onto sat. aq. NaHCO3, extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated. Purification on a SiO2-column (CH2Cl2/MeOH 95:5), afforded the titled compound in 55% yield as a colorless foam. MS: 444.3 (MH+).

Workup

  1. customto reach room temperature
  2. stirringwas stirred for a further 3 h after which time it
  3. customwas evaporated to dryness
  4. dissolutionThe crude residue was redissolved in 5 ml of DMF
  5. stirringThe reaction was stirred for 16 h after which time the mixture
  6. extractionextracted with EtOAc
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification on a SiO2-column (CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-996900ffa1044fb0a64aa75a2ddedb64
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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