Formaldehyde → tert-butyl (6S,7S)-5-methyl-6-{[4-(3-methylphenyl)piperazin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxylate

HRID 1477378Notes

Reaction equation

HRID 1477378 reaction equation
[C:1]([O:5][C:6]([C@H:8]1[CH2:15][C:12]2([CH2:14][CH2:13]2)[CH2:11][NH:10][C@@H:9]1[C:16]([OH:18])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:29]=2N=N1.[CH3:46][C:47]1[CH:48]=[C:49]([N:53]2[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)[CH:50]=[CH:51][CH:52]=1.C(N(C(C)C)CC)(C)C.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CN(C=O)C>[CH3:29][N:10]1[C@H:9]([C:16]([N:56]2[CH2:57][CH2:58][N:53]([C:49]3[CH:50]=[CH:51][CH:52]=[C:47]([CH3:46])[CH:48]=3)[CH2:54][CH2:55]2)=[O:18])[C@@H:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:15][C:12]2([CH2:13][CH2:14]2)[CH2:11]1

Participants

8

Reactant 6

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 831111-(m-Tolyl)piperazineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5049666Sodium triacetoxyborohydrideHCID 16108946HCID 16108946, compound

Product 1

HCID 67438575tert-butyl (6S,7S)-5-methyl-6-{[4-(3-methylphenyl)piperazin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2.5]octane-6-carboxylic acid of step 1g (25 mg), BOP (45 mg), 1-(3-methylphenyl)piperazine (176 mg) and di-isopropylethylamine (70 μL) in DMF (500 μL) was stirred at RT overnight. Formaldehyde solution (0.5 M in THF/MeCN (1:1), 600 μL) was added to the mixture followed by NaBH(OAc)3 (0.25 M in THF/MeCN (1:1), 1000 μL). The resulting mixture was stirred overnight. The solvents were removed under reduced pressure. The residue was dissolved in ethyl acetate (5 mL). The solution was washed with NaHCO3 (7.5%, 3×1 mL). The organic phase was dried over MgSO4 and filtered and concentrated. The residue was used directly in the next step reaction without further purification.

Workup

  1. stirringThe resulting mixture was stirred overnight
  2. customThe solvents were removed under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (5 mL)
  4. washThe solution was washed with NaHCO3 (7.5%, 3×1 mL)
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was used directly in the next step reaction without further purification

Sources & evidence

ORD record
ord-d92a9c8898594f1baa192f903e123864
Source dataset
uspto-grants-2016_08
Patent number
US09403775B2

Reaction notes

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