Ammonium Chloride → HCID 10031530, compound

HRID 1945099Notes

Reaction equation

HRID 1945099 reaction equation
[CH3:1][O:2][C:3](=[O:25])[C@H:4]1[CH2:8][CH:7]([O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[C:6](=[O:17])[N:5]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C[Si](C)(C)N[Si](C)(C)C.[Li].[C:36]([O:40][C:41]([N:43]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:45]([CH2:52]Br)=[CH:44]1)=[O:42])([CH3:39])([CH3:38])[CH3:37].[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:25])[C@H:4]1[CH2:8][C@:7]([O:9][Si:10]([C:13]([CH3:16])([CH3:14])[CH3:15])([CH3:12])[CH3:11])([CH2:52][C:45]2[C:46]3[C:51](=[CH:50][CH:49]=[CH:48][CH:47]=3)[N:43]([C:41]([O:40][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:42])[CH:44]=2)[C:6](=[O:17])[N:5]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 582475tert-Butyl 3-(bromomethyl)-1H-indole-1-carboxylateHCID 57426343Lithium bis(trimethylsilyl)amideHCID 67375171HCID 67375171, compound

Product 1

HCID 10031530HCID 10031530, compoundYield 51.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

1.45 g (3.9 mmol) of the above N-t-butoxycarbonyl-4-t-butyldimethylsilyloxy-D-pyro-glutamic acid methyl ester were dissolved in 15 ml of anhydrous THF (tetrahydrofuran) in an atmosphere of argon gas. The resulting solution was cooled to −78° C., 2.8 ml (4.8 mmol; 1.7 mM/ml) of LHMDS (lithium hexamethyldisilazane) were added to it, and the mixture was stirred for an hour. A solution obtained by dissolving 1.30 g (4.2 mmol) of N-t-butoxycarbonyl-3-bromomethylindole in 4 ml of THF was added dropwise into the reacted solution and it was stirred at −78° C. for 25 minutes and then at room temperature for two hours. An aqueous solution of ammonium chloride was added to the reacted solution, and extraction was performed twice with 50 ml of ethyl acetate. The organic layer was washed with 50 ml of water and 50 ml of a saturated saline solution and was dried with anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was refined by PTLC (preparative thin-layer chromatography) to yield 1.21 g (2.01 mmol) of N-t-butoxycarbonyl-(4R)-4-t-butyldimethylsilyloxy-4-(N-t-butoxycarbonyl-3-indolylmethyl)-D-pyroglutamic acid methyl ester. Its 1H-NMR spectrum showed a peak marked by a very small amount (several percent) of impurity beside the isomers of the compound.

Workup

  1. customA solution obtained
  2. additionwas added dropwise into the reacted solution and it
  3. stirringwas stirred at −78° C. for 25 minutes
  4. washThe organic layer was washed with 50 ml of water and 50 ml of a saturated saline solution
  5. dry with materialwas dried with anhydrous magnesium sulfate
  6. customThe magnesium sulfate was removed by filtration
  7. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-1090749453bf41f8840e9969158c2fbd
Source dataset
uspto-grants-2013_03
Patent number
US08394970B2

Reaction notes

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