Diisopropylethylamine → 1H-Indole-2-carboxylic acid, 1-[2-[[(1,1-dimethylethoxy)carbonyl]amino]-3-methyl-1-oxobutyl]-2,3-dihydro-, ethyl ester, [S-(R*,R*)]-

HRID 1477166Notes

Reaction equation

HRID 1477166 reaction equation
F[P-](F)(F)(F)(F)F.CN(C)C(F)=[N+](C)C.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH:28]([CH3:30])[CH3:29])[C:25]([OH:27])=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(N(C(C)C)CC)(C)C.[NH:40]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42][C@H:41]1[C:49]([O:51][CH2:52][CH3:53])=[O:50]>C(Cl)Cl.CCOC(C)=O>[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH:28]([CH3:30])[CH3:29])[C:25]([N:40]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42][C@H:41]1[C:49]([O:51][CH2:52][CH3:53])=[O:50])=[O:27])=[O:22])([CH3:17])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 11030625(S)-Indoline-2-carboxylic acid ethyl ester

Product 1

HCID 107154341H-Indole-2-carboxylic acid, 1-[2-[[(1,1-dimethylethoxy)carbonyl]amino]-3-methyl-1-oxobutyl]-2,3-dihydro-, ethyl ester, [S-(R*,R*)]-Yield 56.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

N,N,N′,N′-tetramethylfluoroformamidinium hexafluorophosphate (1.1 g, 4.18 mmol, Eq: 1.6) was added to a solution of (S)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (738 mg, 3.4 mmol, Eq: 1.3) and diisopropylethylamine (1.4 mL, 7.84 mmol, Eq: 3) in DCM (10 mL) and the resulting solution was stirred at rt for 1 h. (S)-Ethyl indoline-2-carboxylate (0.5 g, 2.61 mmol, Eq: 1.00) was added and the reaction mixture was stirred at rt over the weekend. The reaction mixture was diluted with EtOAc (50 mL) and washed with 0.1 M aqueous HCl (50 mL), 0.1 M aqueous NaOH (50 mL) and brine (25 mL). The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 20% EtOAc in hexanes) to give (S)-ethyl 1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)indoline-2-carboxylate (0.58 g), m/z=391 (M+H).

Workup

  1. additionwas added
  2. washwashed with 0.1 M aqueous HCl (50 mL), 0.1 M aqueous NaOH (50 mL) and brine (25 mL)
  3. customThe crude material was purified by flash chromatography (silica gel, 24 g, 0% to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-4be0ba8db82c4ca68a42af5c478c5ed1
Source dataset
uspto-grants-2016_08
Patent number
US09403768B2

Reaction notes

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