Hydrochloric Acid → HCID 71008985, compound

HRID 1626097Notes

Reaction equation

HRID 1626097 reaction equation
[C:1]([O:5][C:6]([N:8](C(OC(C)(C)C)=O)[C:9]1[O:10][CH2:11][C:12]([F:25])([F:24])[C@:13]([C@H:16]2[CH2:18][C@@H:17]2[C:19]([O:21]CC)=[O:20])([CH3:15])[N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl>C(O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[O:10][CH2:11][C:12]([F:24])([F:25])[C@:13]([C@H:16]2[CH2:18][C@@H:17]2[C:19]([OH:21])=[O:20])([CH3:15])[N:14]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 90291436HCID 90291436, compound

Product 1

HCID 71008985HCID 71008985, compoundYield 64.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of (1S,2S)-rel-ethyl 2-((R)-2-(bis(tert-butoxycarbonyl)amino)-5,5-difluoro-4-methyl-5,6-dihydro-4H-1,3-oxazin-4-yl)cyclopropanecarboxylate (519 mg, 1.12 mmol) in ethanol (10 ml) and sodium hydroxide (2M; 2.24 ml, 4.49 mmol) was heated at 40° C. for 90 minutes. Thereafter hydrochloric acid (1N) was added dropwise under cooling with ice until a neutral pH was reached. For the workup, the solvent was removed at reduced pressure, the residue taken up in water and dichloromethane, and the mixture acidified by dropwise addition of hydrochloric acid (1N) under cooling with ice. The aqueous layer which was extracted 3 times with dichloromethane, then sodium chloride was added to the aqueous layer which was extracted again 3 times with dichloromethane. The combined organic layers were dried over sodium sulphate and concentrated at reduced pressure to give the crude (1S,2S)-rel-2-((R)-2-tert-butoxycarbonylamino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-cyclopropane-carboxylic acid (240 mg, 64% yield) which was used in the next step without further purification. MS (ISP): m/z=335.1 [M+H]+.

Workup

  1. temperatureunder cooling with ice until a neutral pH
  2. customFor the workup, the solvent was removed at reduced pressure
  3. additiondichloromethane, and the mixture acidified by dropwise addition of hydrochloric acid (1N)
  4. temperatureunder cooling with ice
  5. extractionThe aqueous layer which was extracted 3 times with dichloromethane
  6. additionsodium chloride was added to the aqueous layer which
  7. extractionwas extracted again 3 times with dichloromethane
  8. dry with materialThe combined organic layers were dried over sodium sulphate
  9. concentrationconcentrated at reduced pressure

Sources & evidence

ORD record
ord-ff6994be1b93485ebb519c480b38e3bc
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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