Potassium bis(trimethylsilyl)amide → HCID 86715375, compound

HRID 630630Notes

Reaction equation

HRID 630630 reaction equation
[CH3:1][CH:2]([CH3:39])[CH2:3][C@H:4]([NH:17][C:18](=[O:38])[C@@H:19]([NH:28][C:29](=[O:37])[CH2:30][N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)=[O:6].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:50][C:51]([O:58][CH2:59][C:60]#[CH:61])([CH3:57])[C:52]([O:54][CH2:55]I)=[O:53]>C1COCC1>[CH3:1][CH:2]([CH3:39])[CH2:3][C@H:4]([N:17]([CH2:55][O:54][C:52](=[O:53])[C:51]([CH3:50])([O:58][CH2:59][C:60]#[CH:61])[CH3:57])[C:18](=[O:38])[C@@H:19]([NH:28][C:29](=[O:37])[CH2:30][N:31]1[CH2:32][CH2:33][O:34][CH2:35][CH2:36]1)[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)=[O:6]

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 86715376HCID 86715376, compoundHCID 86715377HCID 86715377, compound

Product 1

HCID 86715375HCID 86715375, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a light yellow solution of (S)-4-methoxybenzyl 4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanoate (2.16 g. 4.0 mmol) in THF (15 mL) at −50° C. was added KHMDS solution (1 M in THF. 5.0 mL, 5.0 mmol) dropwise maintaining the internal reaction temperature below −50° C. The mixture was stirred for 10 min and a solution of iodomethyl 2-methyl-2-(prop-2-ynyloxy)propanoate (1.58 g, 5.6 mmol) in THF (5.0 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 3 h. The reaction was quenched with methanol (3 mL) and then diluted with ethyl acetate. The resulting mixture was washed with brine and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting oil was purified by flash column chromatography on silica gel (hexanes/ethyl acetate=9:1 to 7:3) to afford compound (major spot, 1.9 g, 68.5% yield) as a colorless oil.

Workup

  1. temperaturedropwise maintaining the internal reaction temperature below −50° C
  2. stirringstirred for 3 h
  3. customThe reaction was quenched with methanol (3 mL)
  4. additiondiluted with ethyl acetate
  5. washThe resulting mixture was washed with brine
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting oil was purified by flash column chromatography on silica gel (hexanes/ethyl acetate=9:1 to 7:3)
  10. customto afford compound (major spot, 1.9 g, 68.5% yield) as a colorless oil

Sources & evidence

ORD record
ord-463aa93c086f40a0a0733f121082141e
Source dataset
uspto-grants-2016_04
Patent number
US09315542B2

Reaction notes

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