Methanol → HCID 42633527, compound

HRID 409430Notes

Reaction equation

HRID 409430 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]([N:14]2[CH2:18][C@@H:17]([N:19]([CH2:32][C:33]3[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[C:35]([C:43]([F:46])([F:45])[F:44])[CH:34]=3)[C:20]3[N:25]=[CH:24][C:23]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)=[CH:22][N:21]=3)[CH2:16][C@H:15]2[CH2:47][CH3:48])=[O:13])[CH2:7][CH2:6]1)=[O:4].O.[OH-].[Li+].O.CO>C1COCC1>[C:3]([CH:5]1[CH2:10][CH2:9][CH:8]([O:11][C:12]([N:14]2[CH2:18][C@@H:17]([N:19]([CH2:32][C:33]3[CH:34]=[C:35]([C:43]([F:44])([F:45])[F:46])[CH:36]=[C:37]([C:39]([F:41])([F:42])[F:40])[CH:38]=3)[C:20]3[N:21]=[CH:22][C:23]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)=[CH:24][N:25]=3)[CH2:16][C@H:15]2[CH2:47][CH3:48])=[O:13])[CH2:7][CH2:6]1)([OH:4])=[O:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 178455820HCID 178455820, compound

Product 1

HCID 42633527HCID 42633527, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid trans-4-methoxycarbonyl-1-cyclohexyl ester (0.101 mmol; 69 mg) and lithium hydroxide monohydrate (0.381 mmol; 16 mg) are dissolved in THF (1 mL), water (0.5 mL) and MeOH (0.1 mL). The solution is stirred for 3 hours at room temperature. The reaction mixture is quenched with aqueous 1M HCl (0.95 mL) and stirred for 15 minutes. To the mixture is added dichloromethane and the organic layer is separated and then concentrated under reduced pressure. The desired product, (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid 4-carboxy-cyclohexyl ester, is obtained in 90% yield (60 mg); ESI-MS m/z: 669 [M+1]+, Retention time 2.13 min (condition A).

Workup

  1. customThe reaction mixture is quenched with aqueous 1M HCl (0.95 mL)
  2. stirringstirred for 15 minutes
  3. additionTo the mixture is added dichloromethane
  4. customthe organic layer is separated
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c1fa44b6eaa3473488e23234bde14f36
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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