Proton sponge → HCID 11027464, compound

HRID 1108480Notes

Reaction equation

HRID 1108480 reaction equation
[C:1]([O:4][CH2:5][CH:6]1[C:14]2[C:9](=[CH:10][C:11]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:12]([NH2:15])[CH:13]=2)[N:8]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:7]1)(=[O:3])[CH3:2].Br[CH:32]([CH3:37])[C:33]([O:35][CH3:36])=[O:34].CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1>C1C=CC=CC=1>[C:1]([O:4][CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:12]([NH:15][CH:32]([C:33]([O:35][CH3:36])=[O:34])[CH3:37])[CH:13]=2)[N:8]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:7]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 95576Methyl 2-bromopropionateHCID 14847355HCID 14847355, compound

Product 1

HCID 11027464HCID 11027464, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

4.95 g (12.0 mmole) of 3S)-3-acetoxymethyl-5-amino-6-benzyloxy-1-t-butoxycarbonylindoline, 1.61 ml (14.4 mmole) of methyl 2-bromopropionate, and 3.09 g (14.4 mmole) of 1,8-bis(dimethylamino)naphthalene were heated to reflux in 18 ml of benzene at 90° C. for 50 hours. The reaction mixture was diluted with benzene, washed with water and saturated brine, dried over anhydrous sodium sulfate, and filtered, followed by condensation to give a residue. The residue was then purified by silica gel column chromatography with changing an eluate from hexane:ethyl acetate (4:1) to hexane:ethyl acetate (2:1) to give 5.82 g of (3S)-3-acetoxymethyl-5-[1-(methoxycarbonyl)ethyl]amino-6-benzyloxy-1-t-butoxycarbonylindoline. Yield, 97%. HRMS: 498.2366 calculated as C27H34N2O7 ; 498.2387 observed.

Workup

  1. washwashed with water and saturated brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customfollowed by condensation
  5. customto give a residue
  6. customThe residue was then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f9ceafeb52844ec4b00764673208e2a0
Source dataset
uspto-grants-2000_05
Patent number
US06066742

Reaction notes

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