Hydrochloric Acid → (S)-3-methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butylamine hydrochloride

HRID 2173859Notes

Reaction equation

HRID 2173859 reaction equation
[CH3:1][CH:2]([CH3:28])[CH2:3][C@H:4]([NH:21][S@](C(C)(C)C)=O)[C:5]1[CH:6]=[N:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[N:9][CH:10]=1.[ClH:29].CCOCC>CO>[ClH:29].[CH3:1][CH:2]([CH3:28])[CH2:3][C@H:4]([NH2:21])[C:5]1[CH:6]=[N:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[N:9][CH:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 68062003(S)-2-methyl-propane-2-sulfinic acid {(S)-3-methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butyl}-amide

Product 1

HCID 67980895(S)-3-methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butylamine hydrochlorideYield 97%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

(S)-2-methyl-propane-2-sulfinic acid {(S)-3-methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butyl}-amide (38.83 g, 93.90 mmol) was dissolved in methanol and transferred to a 3-necked 1 L flask with overhead stirring and internal temperature. A total of 210 mL methanol was added to give a yellow solution. This was placed in an ice bath and at an internal temperature of 8° C., HCl in ether (188 mL, 2.0 M, 376 mmol) was added over 2 min. The temperature went up to 14° C. The ice bath was removed and the reaction stirred for ˜5 min as a yellow solution than as a white slurry. At 30 min, the reaction was rotovapped to dryness and the solid slurried in diethylether (200 mL) for 1 h. The solid was collected by Buchner filtration, washing with additional diethylether. This was suction dried for ˜1 h and then placed on the vacuum pump to give (S)-3-methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butylamine hydrochloride (31.58 g, 97%) as a white solid. 1H NMR (400 MHz, DMSO-d6, δ): 9.19 (s, 2H) 8.78 (br. s., 3H) 8.61 (d, J=8.2 Hz, 2H) 7.93 (d, J=8.4 Hz, 2H) 4.47 (br. s., 1H) 1.84-2.03 (m, 2H) 1.41 (m, 1H) 0.83-0.96 (m, 6H).

Workup

  1. customtransferred to a 3-necked 1 L flask with overhead
  2. customto give a yellow solution
  3. additionwas added over 2 min
  4. customwent up to 14° C
  5. customThe ice bath was removed
  6. stirringthe reaction stirred for ˜5 min as a yellow solution than as a white slurry
  7. waitthe solid slurried in diethylether (200 mL) for 1 h
  8. filtrationThe solid was collected by Buchner filtration
  9. washwashing with additional diethylether
  10. customThis was suction dried for ˜1 h

Sources & evidence

ORD record
ord-edeeb226c3934f9293584b9b94240cd5
Source dataset
uspto-grants-2015_06
Patent number
US09056834B2

Reaction notes

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