Triethylamine → rel-(S)-1-[(3S,4S)-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-3-yl]-1-(2-fluoro-phenyl)-ethylamine

HRID 2178196Notes

Reaction equation

HRID 2178196 reaction equation
C(N(CC)CC)C.[NH2:8][C@@:9]([C@H:18]1[CH2:22][O:21][CH2:20][C@H:19]1[OH:23])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17])[CH3:10].[C:24]([Si:28]([CH3:31])([CH3:30])Cl)([CH3:27])([CH3:26])[CH3:25]>ClCCl.CN(C)C1C=CN=CC=1>[C:24]([Si:28]([CH3:31])([CH3:30])[O:23][C@@H:19]1[CH2:20][O:21][CH2:22][C@@H:18]1[C@:9]([NH2:8])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17])[CH3:10])([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 68158183rel-(3S,4S)-4-((S)-1-amino-1-(2-fluorophenyl)ethyl)tetrahydrofuran-3-ol

Product 1

HCID 68158175rel-(S)-1-[(3S,4S)-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-3-yl]-1-(2-fluoro-phenyl)-ethylamineYield 96.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (8.05 g, 79.6 mmol) was added to a solution of rel-(3S,4S)-4-((S)-1-amino-1-(2-fluorophenyl)ethyl)tetrahydrofuran-3-ol (5.6 g, 24.9 mmol) in dichloromethane (100 ml) at 0° C., then 4-dimethylaminopyridine (1.52 g, 12.4 mmol) followed by tert-butyldimethylchlorosilane (7.49 g, 49.7 mmol). The reaction mixture was stirred at room temperature overnight. For the workup, the reaction mixture was extracted with a saturated solution of sodium hydrogencarbonate and brine. The organic layer was dried over sodium sulphate and evaporated. The crude material was purified by flash chromatography on silica gel using a gradient of heptane and ethyl acetate=100:0 to 50:50 as the eluent. The rel-(S)-1-[(3S,4S)-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-3-yl]-1-(2-fluoro-phenyl)-ethylamine (8.13 g, 96% yield) was obtained as a colorless oil. MS (ISP): m/z=340.1 [M+H]+.

Workup

  1. extractionFor the workup, the reaction mixture was extracted with a saturated solution of sodium hydrogencarbonate and brine
  2. dry with materialThe organic layer was dried over sodium sulphate
  3. customevaporated
  4. customThe crude material was purified by flash chromatography on silica gel using a gradient of heptane and ethyl acetate=100:0 to 50:50 as the eluent

Sources & evidence

ORD record
ord-c915a2630903413ab058456a9df50cfe
Source dataset
uspto-grants-2015_06
Patent number
US09067924B2

Reaction notes

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