tert-Butanol → HCID 178426227, compound

HRID 1044372Notes

Reaction equation

HRID 1044372 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[CH2:12][CH2:11][C@:10]3([CH2:17][CH2:16][CH2:15][NH:14][CH2:13]3)[C:9]2=[O:18])[CH2:4][CH2:3]1.[CH3:19][C:20]1[CH:25]=[CH:24][C:23](I)=[C:22]([F:27])[CH:21]=1.CC(C)([O-])C.[Na+].O1CCOCCOCCOCCOCCOCC1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.C(O)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:27][C:22]1[CH:21]=[C:20]([CH3:19])[CH:25]=[CH:24][C:23]=1[N:14]1[CH2:15][CH2:16][CH2:17][C@@:10]2([C:9](=[O:18])[N:8]([C@H:5]3[CH2:6][CH2:7][C@H:2]([OH:1])[CH2:3][CH2:4]3)[CH2:12][CH2:11]2)[CH2:13]1

Participants

8

Reactant 6

HCID 6386tert-ButanolHCID 2855718-Crown-6HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 2774524Benzene, 2-fluoro-1-iodo-4-methyl-HCID 23676156Sodium t-butoxideHCID 178517864HCID 178517864, compound

Product 1

HCID 178426227HCID 178426227, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A mixture of (5S)-2-(trans-4-hydroxycyclohexyl)-2,7-diazaspiro[4.5]decan-1-one (20 mg, 0.00007 mol) which was prepared using procedures analogous to those described in the synthesis of example 472-a and followed by standard hydrogenation to remove the carbobenzyloxy (Cbz) protecting and, 4-methyl-2-fluoro-1-iodobenzene (21 mg, 0.00009 mol), sodium tert-butoxide (9.98 mg, 0.000104 mol), 1,4,7,10,13,16-hexaoxacyclooctadecane (27.4 mg, 0.000104 mol), 2-(di-tert-butylphosphino)biphenyl (0.8 mg, 0.000003 mol), tris(dibenzylideneacetone)dipalladium(0) (1 mg, 0.000001 mol), in tert-butyl alcohol (1.0 mL, 0.010 mol) was stirred at rt for 18. The crude product was purified by prep-HPLC to afford the desired product. LC-MS: 361.1 (M+H)+.

Workup

  1. customwas prepared
  2. customthose described in the synthesis of example 472-a
  3. customThe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-e18d147941634d9a909532e523b49ff0
Source dataset
uspto-grants-2013_10
Patent number
US08563570B2

Reaction notes

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