Hydrochloric Acid → 2-Amino-2-[5-trifluoromethyl-6-(4-trifluoromethylcyclohexyloxy)-naphthalen-2-yl]-propane-1,3-diol

HRID 2389095Notes

Reaction equation

HRID 2389095 reaction equation
CC1(C)[O:7][CH2:6][C:5]([NH:33]C(=O)OC(C)(C)C)([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:22][CH:23]4[CH2:28][CH2:27][CH:26]([C:29]([F:32])([F:31])[F:30])[CH2:25][CH2:24]4)[C:14]=3[C:18]([F:21])([F:20])[F:19])[CH:9]=2)[CH2:4][O:3]1.CO.Cl.O>>[NH2:33][C:5]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:22][CH:23]3[CH2:28][CH2:27][CH:26]([C:29]([F:30])([F:31])[F:32])[CH2:25][CH2:24]3)[C:14]=2[C:18]([F:20])([F:21])[F:19])[CH:9]=1)([CH2:6][OH:7])[CH2:4][OH:3]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 962WaterHCID 86642890Tert-butyl 2,2-dimethyl-5-(5-(trifluoromethyl)-6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)-1,3-dioxan-5-ylcarbamate

Product 1

HCID 461962462-Amino-2-[5-trifluoromethyl-6-(4-trifluoromethylcyclohexyloxy)-naphthalen-2-yl]-propane-1,3-diolYield 106.8%

Conditions

Temperature
80 °C

Procedure

Tert-butyl 2,2-dimethyl-5-(5-(trifluoromethyl)-6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)-1,3-dioxan-5-ylcarbamate (1000.1 mg, 0.0016906 mol) (impure, assume 100% purity) was dissolved in methanol (30 mL, 0.73 mol), followed by 1 M of hydrogen chloride in water (30 mL, 0.030 mol). The reaction mixture was then heated at 80° C. for 2.5 hours. The solvent was removed under reduced pressure and the crude residue was treated with 4 N HCl in 1,4-dioxane. The solution was stirred for 1 hour and the solvent was then removed under reduced pressure. Ethyl ether was then added and the resulting solid was removed via filtration to give 815 mg of the desired product a white solid (64%). ESI-MS: 417 (M-16)+ 1H NMR (400 MHz, DMSO-d6) δ=8.21-7.97 (m, 3 H), 7.82-7.61 (m, 2 H), 5.57-5.41 (m, 4 H), 5.10 (br. s., 0.61 H), 4.98-4.88 (m, 0.32 H), 3.97-3.72 (m, 1 H), 2.15-1.91 (m, 2 H), 1.82-1.08 (m, 6 H)

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe crude residue was treated with 4 N HCl in 1,4-dioxane
  3. customthe solvent was then removed under reduced pressure
  4. additionEthyl ether was then added
  5. customthe resulting solid was removed via filtration

Sources & evidence

ORD record
ord-fe50b828d7a74300bd70d390a316c96b
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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