HCID 86691106, compound → HCID 86691105, compound

HRID 1773019Notes

Reaction equation

HRID 1773019 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH2:11][CH:10]([O:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH2:9][CH2:8][C:7]=1[O:17][CH:18]([CH2:21][CH2:22][N:23]=[N+]=[N-])[CH2:19][CH3:20])=[O:5])[CH3:2].[H][H]>[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].C(O)C.ClCCl>[CH2:1]([O:3][C:4]([C:6]1[CH2:11][CH:10]([O:12][S:13]([CH3:16])(=[O:14])=[O:15])[CH2:9][CH2:8][C:7]=1[O:17][CH:18]([CH2:21][CH2:22][NH2:23])[CH2:19][CH3:20])=[O:5])[CH3:2]

Participants

6

Reactant 2

HCID 86691106HCID 86691106, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86691105HCID 86691105, compound

Reagents, catalysts & solvents 3

HCID 131709914Lindlars catalystCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

(3R,4S,5R)-4-(diethoxy-phosphorylamino)-3-({1-(2-azido-ethyl}-propoxy)-5-methanesulfonyloxy-cyclohex-1-enecarboxylic acid ethyl ester (46) and Lindlar catalyst in ethanol was added. The flask was charged with hydrogen gas (1 atm) at room temperature. The resulting suspension was vigorously stirred for 24 hours. The reaction mixture was diluted with dichloro methane and the combined organic layers were filtered through a Celite pad. The combined organic phases were dried over Na2SO4 and the combined organic phases were evaporated in a rotary evaporator to yield the (3R,4S,5R)-4-(diethoxy-phosphorylamino)-3-({1-(2-amino-ethyl}-propoxy)-5-methanesulfonyloxy-cyclohex-1-enecarboxylic acid ethyl ester as a pale yellow liquid, which was used without further purification in the next step. (3R,4S,5R)-4-(diethoxy-phosphorylamino)-3-({1-(2-amino-ethyl}-propoxy)-5-methanesulfonyloxy-cyclohex-1-enecarboxylic acid ethyl ester was coupled with Fmoc-PEG-acid (16 atoms) in the presence of EDC, HOBT plus DIPEA in dichloro methane. The solution was stirred over a period of 18 hours the room temperature. The crude product was purified by a silica column chromatography using a 8:2 mixture of dichloro methane and hexane. The combined fractions were evaporated and dried over Na2SO4 and the combined organic phases were evaporated on a rotary evaporator to obtain as (3R,4S,5R)-4-(diethoxy-phosphorylamino)-3-({1-(2-Fmoc-Peg-amide-ethyl}-propoxy)-5-methanesulfonyloxy-cyclohex-1-enecarboxylic acid ethyl ester (47).

Workup

  1. filtrationthe combined organic layers were filtered through a Celite pad
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. customthe combined organic phases were evaporated in a rotary evaporator

Sources & evidence

ORD record
ord-ba6635ef42144f2ea736531412c9bb92
Source dataset
uspto-grants-2016_02
Patent number
US09250238B2

Reaction notes

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