Sodium Bicarbonate → HCID 59382932, compound

HRID 2355412Notes

Reaction equation

HRID 2355412 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:7]=2[C@:13]([C@@H:21]2[CH2:26][CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22]2)([OH:20])[CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH3:19])[CH2:3][CH2:2]1.C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH:1]1([CH2:4][O:5][C:6]2[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:7]=2[C@:13]([C@@H:21]2[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]2)([OH:20])[CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH3:19])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 59383064HCID 59383064, compound

Product 1

HCID 59382932HCID 59382932, compoundYield 42.5%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of (R)-tert-butyl 3-((S)-1-(2-(cyclopropylmethoxy)-3-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate (120 mg) in 20% TFA/CH2Cl2 (20 mL) was stirred at 0° C. for 5 min. The solvent was neutralized by addition of sat'd aq NaHCO3, and the mixture was extracted with CH2Cl2 (3×). The combined organic layers were dried over Na2SO4 and evaporated to give the crude product. LC-MS analysis of the crude product indicated the presence of two isomers (10:1). The crude product was purified by reverse phase prep HPLC to afford the major isomer, (S)-1-(2-(cyclopropylmethoxy)-3-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (40 mg, 42%). 1H NMR (400 MHz, CD4O): 0.36 (m, 2H), 0.63 (m, 2H), 0.86 (m, 1H), 1.55-1.11 (m, 1H), 1.82 (m, 1H), 2.29 (m, 2H), 2.45 (m, 1H), 2.66 (t, 1H), 2.94 (d, 1H), 3.24 (s, 3H), 3.31 (m, 2H), 3.91 (m, 2H), 6.98 (m, 2H), 726 (m, 1H). MS (E/Z): 366 (M+1). In addition, 2-fluoro-6-((S)-1-hydroxy-5-methoxy-1-((R)-piperidin-3-yl)pentyl)phenol was isolated as a byproduct.

Workup

  1. extractionthe mixture was extracted with CH2Cl2 (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. customevaporated
  4. customto give the crude product
  5. customThe crude product was purified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-8c547bfda36e4f56b48a76c3c79e70ae
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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