Triethylamine → HCID 66669456, compound

HRID 1924183Notes

Reaction equation

HRID 1924183 reaction equation
[OH:1][CH2:2][C@@H:3]1[CH2:8][N:7]2[CH2:9][CH2:10][CH2:11][C@H:6]2[C:5](=[O:12])[NH:4]1.C(N(CC)CC)C.[Si:20](Cl)([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21]>CN(C)C=O.CN(C)C1C=CN=CC=1>[CH3:24][C:23]([Si:20]([CH3:22])([CH3:21])[O:1][CH2:2][C@@H:3]1[CH2:8][N:7]2[CH2:9][CH2:10][CH2:11][C@H:6]2[C:5](=[O:12])[NH:4]1)([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 45116030HCID 45116030, compound

Product 1

HCID 66669456HCID 66669456, compoundYield 66.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S,8aS)-3-(hydroxymethyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one (1.49 g, 8.82 mmol) in dimethylformamide (20 mL) was added triethylamine (2.45 mL, 17.6 mmol) and 4-dimethylaminopyridine (90 mg, 0.882 mmol). The solution was cooled in an ice bath and tert-butyldimethylsilyl chloride (2.66 g, 17.6 mmol) was added. The mixture was warmed to room temperature and stirred for 14 h. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The aqueous portion was extracted twice with ethyl acetate. The combined organic portion was dried over sodium sulfate, filtered and concentrated in vacuo to afford a pale brown solid which was triturated with ethyl acetate to afford (3S,8aS)-3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one as an off-white solid (1.74 g, 5.84 mmol, 66% yield). 1H NMR (400 MHz, CDCl3): 6.09-5.90 (m, 1H), 3.86-3.76 (m, 1H), 3.63 (dd, 1H), 3.44 (dd, 1H), 3.25 (t, 1H), 3.10 (ddd, 1H), 2.98-2.90 (m, 1H), 2.68-2.60 (m, 1H), 2.52 (dd, 1H), 2.28-2.18 (m, 1H), 2.06-1.95 (m, 1H), 1.93-1.74 (m, 2H), 0.90 (s, 9H), 0.07 (s, 6H); MS (EI) for C14H28N2O2Si: 285 (MH+).

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe residue was partitioned between ethyl acetate and water
  4. extractionThe aqueous portion was extracted twice with ethyl acetate
  5. dry with materialThe combined organic portion was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a pale brown solid which
  9. customwas triturated with ethyl acetate

Sources & evidence

ORD record
ord-c78084fd295043079e0242157673a638
Source dataset
uspto-grants-2012_05
Patent number
US08178532B2

Reaction notes

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