1-Methyl-2-piperidinemethanol → Methyl(2S)-2-(tert-butoxy)-2-[(22S)-16,17-difluoro-5-(1-hydroxyethyl)-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

HRID 1482117Notes

Reaction equation

HRID 1482117 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([CH:42]=[O:43])[C:38]2=[N:44][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:50][CH2:49][C:16]([CH3:51])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:48])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:47])=[C:28]([F:46])[C:29]=2[C:30]2[CH:45]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:52]N1CCCCC1CO.C[Zn]C>C1(C)C=CC=CC=1>[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([CH:42]([OH:43])[CH3:52])[C:38]2=[N:44][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:14][CH2:15][C:16]([CH3:51])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:48])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:47])=[C:28]([F:46])[C:29]=2[C:30]2[CH:45]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:49][CH2:50]1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 893941-Methyl-2-piperidinemethanolHCID 118316352Methyl(2S)-2-(tert-butoxy)-2-[(22S)-16,17-difluoro-5-formyl-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetateHCID 178477796HCID 178477796, compound

Product 1

HCID 118316353Methyl(2S)-2-(tert-butoxy)-2-[(22S)-16,17-difluoro-5-(1-hydroxyethyl)-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Methyl(2S)-2-(tert-butoxy)-2-[(22S)-16,17-difluoro-5-formyl-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate (0.017 g, 0.024 mmol, 1.0 equiv) and (1-methylpiperidin-2-yl)methanol (3.12 mg, 0.024 mmol, 1.0 equiv) were mixed in 1 mL toluene and concentrated to remove water. Then the mixture was re-dissolved in toluene (1.2 mL). To this solution was added 1 M dimethyl zinc (0.097 mL, 4.0 equiv) and stirred for 1 hour. It was quenched by 1 mL methanol. After concentration, the residue was used as is for the next reaction. LCMS (ESI, M+1): 720.4.

Workup

  1. concentrationconcentrated
  2. customto remove water
  3. dissolutionThen the mixture was re-dissolved in toluene (1.2 mL)
  4. customIt was quenched by 1 mL methanol
  5. concentrationAfter concentration
  6. customas is for the next reaction

Sources & evidence

ORD record
ord-395716d8f1004bd5969d45d2b1543a4e
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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