Oxalyl chloride → HCID 178483652, compound

HRID 1063645Notes

Reaction equation

HRID 1063645 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]([N:9]([CH3:21])[CH2:10][CH2:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]([OH:20])=O)[CH2:14][CH2:13]2)=[O:8])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:30][NH:31][CH2:32][CH2:33][CH2:34][OH:35].[Cl-].COC[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C.C(Cl)Cl.CCN(CC)CC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7](=[O:8])[N:9]([CH2:10][CH2:11][C@H:12]2[CH2:13][CH2:14][C@H:15]([C:18](=[O:20])[N:31]([CH2:32][CH2:33][CH2:34][OH:35])[CH3:30])[CH2:16][CH2:17]2)[CH3:21])=[CH:22][CH:23]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 101489863-(Methylamino)-1-propanolHCID 178483657HCID 178483657, compound

Product 1

HCID 178483652HCID 178483652, compoundYield 77.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 1.02 g (3.00 mmol) of trans-4-{2-[(4-chloro-phenoxycarbonyl)-methyl-amino]-ethyl}-cyclohexanecarboxylic acid in 30 mL of CH42Cl2 was treated at RT with 2 drops of DMF, followed by 0.28 mL (3.30 mmol, 1.1 eq) of oxalyl chloride within 5 min, and stirring was continued for 90 min. The solution was evaporated, redissolved in 15 mL of CH2Cl2 and added to a solution of 0.80 g (9.00 mmol, 3 eq) of 3-(methylamino)-1-propanol [Powell et al., Synthesis (4) 338-340 (1986)]and 2.09 mL (15.00 mmol, 5 eq) of Et3N in 12 mL of CH2Cl2 at 0° C. The reaction was kept at RT for 1 h then partitioned between Et2O (×3)/ aqueous saturated NaHCO3. The organic phases were washed once with aqueous 10% NaCl, dried over Na2SO4 and evaporated. Purification by flash-chromatography on 90 g silica gel (EtOAc:CH2Cl2 1:1 to 4:1) gave 0.95 g (77%) of pure trans-(2-{4-[(3-hydroxy-propyl)-methyl-carbamoyl]-cyclohexyl}-ethyl)-methyl-carbamic acid 4-chloro-phenyl ester, MS: 411 (MH+, 1Cl).

Workup

  1. customThe solution was evaporated
  2. dissolutionredissolved in 15 mL of CH2Cl2
  3. waitThe reaction was kept at RT for 1 h
  4. customthen partitioned between Et2O (×3)/ aqueous saturated NaHCO3
  5. washThe organic phases were washed once with aqueous 10% NaCl
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customPurification by flash-chromatography on 90 g silica gel (EtOAc:CH2Cl2 1:1 to 4:1)

Sources & evidence

ORD record
ord-9bc297f6f31e46cf926e04a01884d473
Source dataset
uspto-grants-2005_11
Patent number
US06965048B2

Reaction notes

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