Lithium Hexamethyldisilazide → HCID 67151379, compound

HRID 1473725Notes

Reaction equation

HRID 1473725 reaction equation
C(OC([NH:8][C@@H:9]([CH2:17][CH2:18][CH2:19][C:20]([O:22]C(C)(C)C)=[O:21])[C:10]([O:12]C(C)(C)C)=[O:11])=O)(C)(C)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:37]([C:39]1[CH:46]=[CH:45][C:42]([CH2:43]Br)=[CH:41][C:40]=1[F:47])#[N:38]>C1COCC1>[NH2:8][C@@H:9]([CH2:17][CH2:18][CH:19]([CH2:43][C:42]1[CH:45]=[CH:46][C:39]([C:37]#[N:38])=[C:40]([F:47])[CH:41]=1)[C:20]([OH:22])=[O:21])[C:10]([OH:12])=[O:11]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27784664-Cyano-3-fluorobenzyl bromideHCID 86678441HCID 86678441, compound

Product 1

HCID 67151379HCID 67151379, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

1.49 g (4 mmol) of di-tert-Butyl (2S)-2-[(tert-butoxycarbonyl)amino]hexanedioate 7a were dissolved in 50 mL of THF and cooled to −70° C. 8.8 mL (8.8 mmol) of a 1M solution of lithium bis(trimethylsilyl)amide in THF were added dropwise over a period of two hours at this temperature and the mixture was stirred at −70° C. for another 2 hours. 0.985 g (4.6 mmol) of 4-Cyano-3-fluorobenzyl bromide were then added dropwise, and after 2 h at this temperature, the cooling bath was removed and 20 mL of 2N aqueous hydrochloric acid and 100 mL of dichloromethane added. The organic phase was separated off, washed with water until neutral, dried over sodium sulphate and filtered, and the filtrate was concentrated. The crude product obtained in this manner was chromatographed on silica gel using a hexane/ethyl acetate gradient, and the appropriate fractions were combined and concentrated (150 mg) MS (ESIpos): m/z=507 [M+H]+

Workup

  1. waitafter 2 h at this temperature
  2. customthe cooling bath was removed
  3. addition20 mL of 2N aqueous hydrochloric acid and 100 mL of dichloromethane added
  4. customThe organic phase was separated off
  5. washwashed with water until neutral,
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-0bfdb9c7907a4d5f9ac15e286132e1f4
Source dataset
uspto-grants-2015_04
Patent number
US09017645B2

Reaction notes

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