Cyclopropylacetylene → (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide

HRID 389405Notes

Reaction equation

HRID 389405 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:11]1([C:14]#[CH:15])[CH2:13][CH2:12]1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([C@@:26]23[C:32]([CH3:34])([CH3:33])[C@@:29]([CH3:35])([CH2:30][CH2:31]2)[C:28](=[O:36])[O:27]3)=[O:25])=[C:19]([C:37](=[O:42])[C:38]([F:41])([F:40])[F:39])[CH:18]=1>C1COCC1>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([C@@:26]23[C:32]([CH3:33])([CH3:34])[C@@:29]([CH3:35])([CH2:30][CH2:31]2)[C:28](=[O:36])[O:27]3)=[O:25])=[C:19]([C@@:37]([OH:42])([C:15]#[C:14][CH:11]2[CH2:13][CH2:12]2)[C:38]([F:39])([F:40])[F:41])[CH:18]=1

Participants

5

Reactant 3

HCID 138823CyclopropylacetyleneHCID 2733832Lithium HexamethyldisilazideHCID 66888235(1S,4R)-N-(4-chloro-2-(2,2,2-trifluoroacetyl)phenyl)-4,7,7-trimethyl-3-oxo-2-ox abicyclo[2.2.1]heptane-1-carboxamide

Product 1

HCID 50916497(1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

Procedure

1M LiHMDS (7.4 mL, 7.4 mmol) was added slowly to a solution of cyclopropyl acetylene (0.49 g, 7.4 mmol) in THF (4 mL) in an ice-salt bath under argon, and then (1S, 4R)-N-(4-chloro-2-(2,2,2-trifluoroacetyl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide (9, 1 g., 2.48 mmol) in THF (1.5 mL) was added slowly. The mixture was stirred at −15° C. for 20 minutes. TLC showed the formation of the product. The reaction mixture was worked up similarly to the example 6, and (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide (10) was isolated as an off-white solid. 1H NMR spectrum of the product was identical to that of Example 5.

Sources & evidence

ORD record
ord-890e099f406f4a138498d9ae8eb2df26
Source dataset
uspto-grants-2013_02
Patent number
US08378143B2

Reaction notes

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