Lithium hydroxide, monohydrate → HCID 77108133, compound

HRID 1846981Notes

Reaction equation

HRID 1846981 reaction equation
O.[OH-].[Li+].[C:4]([S:8]([CH2:11][C@@H:12]([N:16]1[C@H:21]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([F:29])[CH:23]=2)[C@@H:20]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=2)[CH2:19][C@@:18]([CH2:38][C:39]([NH:41][C:42]2[CH:51]=[CH:50][C:45]([C:46]([O:48]C)=[O:47])=[C:44]([O:52][CH3:53])[CH:43]=2)=[O:40])([CH3:37])[C:17]1=[O:54])[CH:13]1[CH2:15][CH2:14]1)(=[O:10])=[O:9])([CH3:7])([CH3:6])[CH3:5]>O.O1CCCC1.CO>[C:4]([S:8]([CH2:11][C@@H:12]([N:16]1[C@H:21]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([F:29])[CH:23]=2)[C@@H:20]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=2)[CH2:19][C@@:18]([CH2:38][C:39]([NH:41][C:42]2[CH:51]=[CH:50][C:45]([C:46]([OH:48])=[O:47])=[C:44]([O:52][CH3:53])[CH:43]=2)=[O:40])([CH3:37])[C:17]1=[O:54])[CH:13]1[CH2:15][CH2:14]1)(=[O:10])=[O:9])([CH3:7])([CH3:5])[CH3:6]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86731829HCID 86731829, compound

Product 1

HCID 77108133HCID 77108133, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of lithium hydroxide monohydrate (18.2 g, 433 mmol) in water (295 mL) was added to a solution of methyl 4-(2-((3R,5R,6S)-1-((S)-2-(tert-butylsulfonyl)-1-cyclopropylethyl)-6-(4-chloro-3-fluorophenyl)-5-(3-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetamido)-2-methoxybenzoate (164.9 g, 217 mmol, Example 5, Step A) in tetrahydrofuran (591 mL) and methanol (197 mL) at room temperature. After stirring for 15 hours at room temperature, a trace amount of the ester remained, so the reaction mixture was heated at 50° C. for 1 hour. When the reaction was complete, the mixture was concentrated under a vacuum to remove the tetrahydrofuran and methanol. The thick mixture was diluted with water (1 L) and 1 M hydrochloric acid (1 L) was added. The resulting white solid was collected by vacuum filtration in a Büchner funnel. The vacuum was removed, and water (1 L) was added to the filter cake. The material was stirred with a spatula to suspend it evenly in the water. The liquid was then removed by vacuum filtration. This washing cycle was repeated three more times to provide a white solid. The solid was dried under vacuum at 45° C. for 3 days to provide the title compound as a white solid.

Workup

  1. temperaturewas heated at 50° C. for 1 hour
  2. concentrationthe mixture was concentrated under a vacuum
  3. customto remove the tetrahydrofuran and methanol
  4. additionThe thick mixture was diluted with water (1 L) and 1 M hydrochloric acid (1 L)
  5. additionwas added
  6. filtrationThe resulting white solid was collected by vacuum filtration in a Büchner funnel
  7. customThe vacuum was removed
  8. additionwater (1 L) was added to the filter cake
  9. stirringThe material was stirred with a spatula
  10. customThe liquid was then removed by vacuum filtration
  11. customto provide a white solid
  12. customThe solid was dried under vacuum at 45° C. for 3 days

Sources & evidence

ORD record
ord-a5d5c55d6f4b4d39b35376dd69d374bc
Source dataset
uspto-grants-2015_02
Patent number
US08952036B2

Reaction notes

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