Trifluoroacetic acid → (S)-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3'-(methylsulfonyl)-5-propyl-[1,1'-biphenyl]-2-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate

HRID 1499234Notes

Reaction equation

HRID 1499234 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:29][CH2:28][C:11]3([CH2:15][N:14](C(OC(C)(C)C)=O)[C@H:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:30][C@H:31]([C:36]2[CH:41]=[CH:40][C:39]([CH2:42][CH2:43][CH3:44])=[CH:38][C:37]=2[C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([S:51]([CH3:54])(=[O:53])=[O:52])[CH:46]=2)[C:32]([F:35])([F:34])[F:33])[N:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:9][CH2:10][C:11]3([CH2:15][NH:14][C@H:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:12]3)[CH2:28][CH2:29]2)[CH:5]=[C:4]([O:30][C@H:31]([C:36]2[CH:41]=[CH:40][C:39]([CH2:42][CH2:43][CH3:44])=[CH:38][C:37]=2[C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([S:51]([CH3:54])(=[O:53])=[O:52])[CH:46]=2)[C:32]([F:35])([F:33])[F:34])[N:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117951871(S)-2-tert-butyl 3-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3'-(methylsulfonyl)-5-propyl-[1,1'-biphenyl]-2-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

Product 1

HCID 131734254(S)-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3'-(methylsulfonyl)-5-propyl-[1,1'-biphenyl]-2-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-tert-butyl 3-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3′-(methylsulfonyl)-5-propyl-[1,1′-biphenyl]-2-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate in CH2Cl2 (4 mL) was added TFA (2.0 mL) dropwise at 0° C. The reaction mixture was stirred at RT for 2 h, then concentrated in vacuo. The pH was adjusted to 7-8 with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with CH2Cl2, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column (CH2Cl2/MeOH) provided (S)-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3′-(methylsulfonyl)-5-propyl-[1,1′-biphenyl]-2-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate as a white solid.

Workup

  1. concentrationconcentrated in vacuo
  2. extractionThe aqueous layer was extracted with CH2Cl2
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by normal phase silica gel column (CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-a1bb50c1b8ae42e0b47dfd44ded4d412
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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