Benzamide → N-[(3S,4R)-3-Hydroxy-2,2-dimethyl-6-(trifluoromethoxy)-chroman-4-yl]-4-chloro-2-nitrobenzamide

HRID 483752Notes

Reaction equation

HRID 483752 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1.S(Cl)(Cl)=O.[NH2:18][C@@H:19]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:29][C:30]([F:33])([F:32])[F:31])[CH:27]=2)[O:22][C:21]([CH3:35])([CH3:34])[C@H:20]1[OH:36].C(N(CC)CC)C.C(N)(=O)C1C=CC=CC=1>C1C=CC=CC=1.ClCCl>[OH:36][C@H:20]1[C@H:19]([NH:18][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=2[N+:11]([O-:13])=[O:12])[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:29][C:30]([F:33])([F:31])[F:32])[CH:27]=2)[O:22][C:21]1([CH3:35])[CH3:34]

Participants

8

Reactant 5

HCID 2331BenzamideHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 804754-Chloro-2-nitrobenzoic acidHCID 15020328(3S,4R)-4-Amino-2,2-dimethyl-6-(trifluoromethoxy)-chroman-3-ol

Product 1

HCID 67753925N-[(3S,4R)-3-Hydroxy-2,2-dimethyl-6-(trifluoromethoxy)-chroman-4-yl]-4-chloro-2-nitrobenzamideYield 43.4%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent

Procedure

4-Chloro-2-nitrobenzoic acid (2.02 g, 10 mmol) was converted to the corresponding acid chloride by refluxing in benzene (30 mL) with thionyl chloride (2.38 g, 20 mmol) for 2 hours. The crude mixture was concentrated in vacuo and diluted with dichloromethane (10 mL). This solution was added to a cooled solution of (3S,4R)-4-amino-2,2-dimethyl-6-(trifluoromethoxy)-chroman-3-ol (2.75 g, 10 mmol), triethylamine (1.39 mL, 10 mmol) and dichloromethane (25 mL). The crude benzamide was worked-up in a method similar to that in Example 1 and chromatographed (1:1 hexanes/ethyl acetate) to afford 2.0 g (43%) of white solid: m.p. 64°-66° C.; 1H NMR (DMSO-d6): δ9.24 (d, 1H), 8.19 (s, 1H), 7.96 (d, 1H), 7.83 (d, 1H), 7.29 (s, 1H), 7.18 (d, 1H), 6.86 (d, 1H), 5.88 (d, 1H), 4.94 (br t, 1H), 3.64 (dd, 1H), 1.42 (s, 3H), 1.19 (s, 3H).

Workup

  1. concentrationThe crude mixture was concentrated in vacuo
  2. additiondiluted with dichloromethane (10 mL)
  3. customchromatographed (1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-f20792abb8c24c65808702ccdb28a5fb
Source dataset
uspto-grants-1993_07
Patent number
US05225566

Reaction notes

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