Ethanol → Neopentyl glycol

HRID 1054699Notes

Reaction equation

HRID 1054699 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]([O:6][CH2:7][C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:4]([O:22][CH3:23])[CH:3]=1.[Cl:24][C:25]1[CH:33]=[C:32]2[C:28]([C:29]([C:34]([O:36][CH3:37])=[O:35])=[CH:30][NH:31]2)=[CH:27][C:26]=1B1[O:43][CH2:42][C:41]([CH3:45])([CH3:44])[CH2:40][O:39]1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[C:16]([O:15][C:13]([N:9]1[CH2:10][CH2:11][CH2:12][C@H:8]1[CH2:7][O:6][C:5]1[CH:20]=[CH:21][C:2]([C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][C:25]=2[Cl:24])[NH:31][CH:30]=[C:29]3[C:34]([O:36][CH3:37])=[O:35])=[CH:3][C:4]=1[O:22][CH3:23])=[O:14])([CH3:19])([CH3:18])[CH3:17].[OH:39][CH2:40][C:41]([CH3:45])([CH2:42][OH:43])[CH3:44]

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylateHCID 86698695(S)-tert-butyl 2-((4-bromo-2-methoxyphenoxy)methyl)pyrrolidine-1-carboxylate

Product 2

HCID 31344Neopentyl glycolHCID 86698696(S)-methyl 5-(4-((1-(tert-butoxycarbonyl)pyrrolidin-2-yl)methoxy)-3-methoxyphenyl)-6-chloro-1H-indole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-tert-butyl 2-((4-bromo-2-methoxyphenoxy)methyl)pyrrolidine-1-carboxylate (77 mg, 0.20 mmol) in toluene (1.5 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (77 mg, 0.24 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (6.7 mg, 0.0080 mmol), ethanol (absolute, 0.5 mL), and potassium carbonate (2 M solution in water, 0.4 mL, 0.80 mmol). Nitrogen was bubbled through the mixture for 20 min. The mixture was then sealed and heated to 90° C. After 18 h, the mixture was allowed to cool to 23° C., diluted with ethyl acetate (5 mL), and filtered through Celite. The filtrate was dried over sodium sulfate and concentrated in vacuo. Purification by column chromatography (silica gel, 0-50% ethyl acetate in heptane) afforded the title compound contaminated with neopentyl glycol.

Workup

  1. customNitrogen was bubbled through the mixture for 20 min
  2. customThe mixture was then sealed
  3. temperatureto cool to 23° C.
  4. additiondiluted with ethyl acetate (5 mL)
  5. filtrationfiltered through Celite
  6. dry with materialThe filtrate was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (silica gel, 0-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-3ad4330f4049490eaa67b19d8e64018d
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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