Formic Acid → (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-((S)-2-carboxy-pyrrolidin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 2267244Notes

Reaction equation

HRID 2267244 reaction equation
[Li+].[OH-].[O:3]=[C:4]1[N:10]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C@H:20]([CH2:38][C:39]3[CH:44]=[C:43]([C:45]([F:48])([F:47])[F:46])[C:42]([NH2:49])=[C:41]([Cl:50])[CH:40]=3)[C:21]([N:23]3[CH2:28][CH2:27][CH:26]([N:29]4[CH2:33][CH2:32][CH2:31][C@H:30]4[C:34]([O:36]C)=[O:35])[CH2:25][CH2:24]3)=[O:22])=[O:18])[CH2:13][CH2:12]2)[CH2:9][CH2:8][C:7]2[CH:51]=[CH:52][CH:53]=[CH:54][C:6]=2[NH:5]1.C(O)=O>O.C1COCC1>[O:3]=[C:4]1[N:10]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C@H:20]([CH2:38][C:39]3[CH:44]=[C:43]([C:45]([F:47])([F:46])[F:48])[C:42]([NH2:49])=[C:41]([Cl:50])[CH:40]=3)[C:21]([N:23]3[CH2:24][CH2:25][CH:26]([N:29]4[CH2:33][CH2:32][CH2:31][C@H:30]4[C:34]([OH:36])=[O:35])[CH2:27][CH2:28]3)=[O:22])=[O:18])[CH2:13][CH2:12]2)[CH2:9][CH2:8][C:7]2[CH:51]=[CH:52][CH:53]=[CH:54][C:6]=2[NH:5]1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 3939Lithium HydroxideHCID 16045719(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-((S)-2-methoxycarbonyl-pyrrolidin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 16045961(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-((S)-2-carboxy-pyrrolidin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2.9 mg (0.12 mmol) LiOH in 1 mL water was added to a solution of 60 mg (0.08 mmol) (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-((S)-2-methoxycarbonyl-pyrrolidin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate in 3 mL THF and the reaction mixture was stirred overnight at RT. The solvent was eliminated in the nitrogen stream, the residue was taken up in 1 mL water, formic acid was added until an acidic reaction was obtained and the mixture was exhaustively extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and evaporated down i. vac. The residue was taken up in a little water and acetonitrile and freeze-dried.

Workup

  1. customwas obtained
  2. extractionthe mixture was exhaustively extracted with EtOAc
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated down i
  6. customfreeze-dried

Sources & evidence

ORD record
ord-bd29852e4f72444e82dca49b6cf5efac
Source dataset
uspto-grants-2010_12
Patent number
US07858622B2

Reaction notes

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