Ammonium Chloride → HCID 131728960, compound

HRID 335506Notes

Reaction equation

HRID 335506 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:12][C:13]([O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])=[O:14])=[C:7]([CH3:11])[NH:8]2)=[CH:4][C:3]=1[O:22][CH3:23].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:34][C:35]1[S:39][C:38]([C:40](Cl)=[O:41])=[CH:37][CH:36]=1.[Cl-].[NH4+]>O1CCCC1.C1(C)C=CC=CC=1.CN(C)P(N(C)C)(N(C)C)=O>[CH3:21][Si:18]([CH3:20])([CH3:19])[CH2:17][CH2:16][O:15][C:13](=[O:14])[CH2:12][C:6]1[C:5]2[C:9](=[CH:10][C:2]([F:1])=[C:3]([O:22][CH3:23])[CH:4]=2)[N:8]([C:40]([C:38]2[S:39][C:35]([Cl:34])=[CH:36][CH:37]=2)=[O:41])[C:7]=1[CH3:11]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 5892235-Chlorothiophene-2-carbonyl ChlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 57421516HCID 57421516, compound

Product 1

HCID 131728960HCID 131728960, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Procedure

In a dry flask 2-trimethylsilylethyl (6-fluoro-5-methoxy-2-methyl-1H-indol-3-yl)acetate (4, R1=H=B, R2=CH3, R3=F, R4=CH2CH2Si(CH3)3), (1.0 g, 2.96 mmol) was dissolved in tetrahydrofuran (THF) (10 mL) and hexamethylphosphoramide (HMPA) (1 mL) and cooled to −78° C. Potassium bis(trimethylsilyl)amide 0.5M in toluene (6.52 mL) was added and the reaction was stirred for 30 minutes. 5-Chlorothiophene-2-carbonyl chloride (562 mg, 3.1 mmol) in 3 mL of THF was added and the reaction was stirred for 0.5 hours at −78° C. and 0.5 hours at 0° C., and then treated with saturated ammonium chloride (20 mL) and the reaction extracted with ethyl acetate (3×30 mL), dried over MgSO4 and concentrated to give a thick oil which was purified by chromatography to afford 2-trimethylsilylethyl-{1-[(5chlorothien-2-yl)carbonyl]-6-fluoro-5-methoxy-2-methyl-1H-indol-3-yl}acetate (5, R1=H=B, R2=CH3, R3=F, R4=CH2CH2Si(CH3)3, A=5-chlorothiophene). (600 mg, 1.24 mmol, 42%, >99% pure) as light yellow oil; 1H-NMR (CDCl3/300 MHz) consistent with the assigned structure.

Workup

  1. stirringthe reaction was stirred for 0.5 hours at −78° C. and 0.5 hours at 0° C.
  2. extractionthe reaction extracted with ethyl acetate (3×30 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customto give a thick oil which
  6. customwas purified by chromatography

Sources & evidence

ORD record
ord-95902ea84ab14e67bdfa0848dc1b785f
Source dataset
uspto-grants-2014_11
Patent number
US08884020B2

Reaction notes

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