Triethylamine → (7S,9aR)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrazino[2,1-c][1,4]oxazine

HRID 2245405Notes

Reaction equation

HRID 2245405 reaction equation
C1[C@H]2CN[C@H](CO)CN2CCO1.C1[C@@H]2CN[C@H](CO)CN2CCO1.CCN(CC)CC.[CH3:32][C:33]([Si:36]([CH3:50])([CH3:49])[O:37][CH2:38][C@@H:39]1[CH2:48][N:47]2[C@H:42]([CH2:43][O:44][CH2:45][CH2:46]2)[CH2:41][NH:40]1)([CH3:35])[CH3:34]>ClCCl>[CH3:35][C:33]([Si:36]([CH3:50])([CH3:49])[O:37][CH2:38][C@@H:39]1[CH2:48][N:47]2[C@@H:42]([CH2:43][O:44][CH2:45][CH2:46]2)[CH2:41][NH:40]1)([CH3:32])[CH3:34]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 59215768(7S,9AS)-7-(((tert-butyldimethylsilyl)oxy)methyl)octahydropyrazino[2,1-c][1,4]oxazineHCID 59215831((7S,9aS)-Octahydropyrazino[2,1-c][1,4]oxazin-7-yl)methanolHCID 66658788(7S, 9aR)-octahydropyrazino[2,1-c][1,4]oxazin-7-ylmethanol

Product 1

HCID 59215815(7S,9aR)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrazino[2,1-c][1,4]oxazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(7S, 9aR)-octahydropyrazino[2,1-c][1,4]oxazin-7-ylmethanol and (7S, 9aS) -octahydropyrazino[2,1-c][1,4]oxazin-7-ylmethanol (D21) (315 mg,1.83 mmol) was dissolved in 10 mL of anhydrous dichloromethane and treated with Et3N (600 μL, 4.30 mmol) and TDBMSCI (590 mg, 3.91 mmol). The reaction was stirred overnight at room temperature (17 h). It was diluted with dichloromethane (30 mL) and extracted with sat. NaHCO3 (2×20 mL). TLC analysis (EtOAc: MeOH 95:5) showed 2 main products. The organics were dried and the solvent removed leaving an oil, which was purified by flash chromatography (silica, EtOAc→EtOAc:MeOH 90:10). Isolated two products: (7S,9aS)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrazino[2,1-c][1,4]oxazine (D22), 253 mg. Direct MS: m/z=287 (M+1).

Workup

  1. extractionextracted with sat. NaHCO3 (2×20 mL)
  2. customThe organics were dried
  3. customthe solvent removed
  4. customleaving an oil, which
  5. customwas purified by flash chromatography (silica, EtOAc→EtOAc:MeOH 90:10)
  6. customIsolated two products

Sources & evidence

ORD record
ord-4b86263f74c74e9f8c07c8beb6e108ef
Source dataset
uspto-grants-2010_03
Patent number
US07683056B2

Reaction notes

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