Water → (2S)-2-tert.-Butoxycarbonylamino-5-{2-[4-(2-fluoro-ethoxy)-phenyl]-ethyl}-hexanedioic acid di-tert.-butyl ester

HRID 591315Notes

Reaction equation

HRID 591315 reaction equation
[F:1][CH2:2][CH2:3]I.CN(C)C=O.[C:10]([O:14][C:15](=[O:44])[C@@H:16]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:17][CH2:18][CH:19]([CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1)[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([CH3:13])([CH3:12])[CH3:11].O>C(OCC)(=O)C>[C:10]([O:14][C:15](=[O:44])[C@@H:16]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:17][CH2:18][CH:19]([CH2:27][CH2:28][C:29]1[CH:30]=[CH:31][C:32]([O:35][CH2:3][CH2:2][F:1])=[CH:33][CH:34]=1)[C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])([CH3:11])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 69804Ethane, 1-fluoro-2-iodo-HCID 70977973Di-tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-5-[2-(4-hydroxyphenyl)ethyl]hexanedioate

Product 1

HCID 89156295(2S)-2-tert.-Butoxycarbonylamino-5-{2-[4-(2-fluoro-ethoxy)-phenyl]-ethyl}-hexanedioic acid di-tert.-butyl esterYield 60.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

53 mg (0.30 mmol) 1-Fluoro-2-iodoethane were dissolved in 5 ml dimethylformamide 98 mg (0.71 mmol) potassium carbonate and 100 mg (0.20 mmol) (2S,5RS)-2-tert.-Butoxycarbonylamino-5-[2-(4-hydroxy-phenyl)-ethyl]-hexanedioic acid di-tert.-butyl ester added. The mixture was stirred at room temperature over night. For workup, water and ethyl acetate were added, the phases separated and the water extracted with ethyl acetate twice. Combined organic phases were dried (Na2SO4), filtered and evaporated. The raw product was absorbed on Isolute and chromatographed on a Biotage Isolera system (SNAP NH 110 g, A=n-hexane, B=ethyl acetate, A 2 CV, A to 47% B in 9.4 CV, 5 CV 50% B, 50 mL/min, Fr. a 22 mL). Fractions 29 to 32 were collected to give 65 mg (59%) of (2S,5RS)-2-tert.-Butoxycarbonylamino-5-{2-[4-(2-fluoro-ethoxy)-phenyl]-ethyl}-hexanedioic acid di-tert.-butyl ester as clear oil.

Workup

  1. customthe phases separated
  2. extractionthe water extracted with ethyl acetate twice
  3. dry with materialCombined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe raw product was absorbed on Isolute
  7. customchromatographed on a Biotage Isolera system (SNAP NH 110 g
  8. customFractions 29 to 32 were collected

Sources & evidence

ORD record
ord-83526803008c4e6a90721946b4dcf299
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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