4-Methylbenzoyl Chloride → HCID 71236977, compound

HRID 2173685Notes

Reaction equation

HRID 2173685 reaction equation
[C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([C:7](Cl)=[O:8])=[CH:3][CH:2]=1.[OH:11][CH2:12][CH2:13][CH2:14][N:15]([CH3:33])[C:16](=[O:32])[O:17][CH2:18][CH:19]1[C:31]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2>N1C=CC=CC=1>[CH3:10][C:1]1[CH:6]=[CH:5][C:4]([C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH3:33])[C:16](=[O:32])[O:17][CH2:18][CH:19]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[C:26]3[C:31]2=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:8])=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 134054-Methylbenzoyl ChlorideHCID 71236895HCID 71236895, compound

Product 1

HCID 71236977HCID 71236977, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of 9-fluorenylmethoxycarbonyl chloride (15.22 g, 58.85 mmol) in dichloromethane (100 ml) was added over 1 h to an ice-cooled solution of 3-methylamino-1-propanol (5.25 g, 58.85 mmol) and triethylamine (9.0 ml, 64.74 mmol) in dichloromethane (50 ml). The resultant suspension was left overnight at −18° C., and then diluted with brine. The organic phase was separated, dried over MgSO4 and concentrated in vacuo. The residue was purified on silica eluting with 1:4 ethyl acetate/dichloromethane to give (9H-fluoren-9-yl)methyl 3-hydroxypropylmethylcarbamate (100% yield). p-Toluoyl chloride (4.26 g, 27.56 mmol) was added dropwise over 10 min to an ice-cooled solution of (9H-fluoren-9-yl)methyl 3-hydroxypropylmethylcarbamate (7.8 g, 25.05 mmol) in pyridine (100 ml). The resultant mixture NA as stirred for 2 h at 0° C., concentrated in vacuo and redissolved in ethyl acetate. The solution was washed with 10% citric acid and brine, then separated, dried over MgSO4 and concentrated in vacuo. The residue was purified on silica eluting with 30% ethyl acetate/hexane to give (9H-fluoren-9-yl)methyl 3-(4-methylbenzoyloxy)propylmethylcarbamate (97% yield). A solution of (9H-fluoren-9-yl)methyl 3-(4-methylbenzoyloxy)propylmethylcarbamate (0.91 g, 2.12 mmol) and triethylamine (5.0 ml) in DMF (5 ml) was stirred for 1 h at +80° C. The resultant mixture was cooled to room temperature and compound 1 (2.01 g, 1.74 mmol) was added. The reaction was diluted with DMF (5), stirred for 2 days, and then diluted with ether (100 ml). The precipitated solid was isolated by filtration, washed with ether and vacuum dried to afford compound 2b (89% yield) as a pale solid, which was sufficiently pure to be used in the next step without additional purification.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionredissolved in ethyl acetate
  3. washThe solution was washed with 10% citric acid and brine
  4. customseparated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on silica eluting with 30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-b7c9485a2c4643b1ab73948fff6a16b6
Source dataset
uspto-grants-2015_06
Patent number
US09056887B2

Reaction notes

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