Acetic Acid → HCID 66546800, compound

HRID 73056Notes

Reaction equation

HRID 73056 reaction equation
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([N:13]2[CH2:18][CH2:17][C:16]3([O:23][CH:22]([CH2:24][O:25][CH3:26])[CH2:21][NH:20][CH2:19]3)[CH2:15][CH2:14]2)=[O:12])=[CH:7][C:6]=1[CH3:27])([CH3:3])[CH3:2].[C:28]1(=O)[CH2:31][CH2:30][CH2:29]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C.CC(OC)(C)C>[CH:28]1([N:20]2[CH2:19][C:16]3([CH2:15][CH2:14][N:13]([C:11]([C:8]4[CH:9]=[CH:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[C:6]([CH3:27])[CH:7]=4)=[O:12])[CH2:18][CH2:17]3)[O:23][CH:22]([CH2:24][O:25][CH3:26])[CH2:21]2)[CH2:31][CH2:30][CH2:29]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 68291762HCID 68291762, compound

Product 1

HCID 66546800HCID 66546800, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A solution of (4-isopropoxy-3-methyl-phenyl)-[10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone (343 mg, 0.912 mmol) and cyclobutanone (96.0 mg, 1.36 mmol) in dichloroethane (3 mL) was treated with acetic acid (78 μL, 1.4 mmol) and stirred for 30 min. NaBH(OAc)3 (387 mg, 1.82 mmol) was added and the reaction mixture stirred for 16 h. The reaction mixture was diluted with MTBE and washed with 1N NaOH (100 mL). The organic layer was separated and washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Silica gel chromatography (5-80% ethyl acetate/hexane) provided (4-cyclobutyl-2-(methoxymethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone (330 mg, 84%). ESI-MS m/z calc. 430.3. Found 431.3 (M+1)+; Retention time: 1.24 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.19 (d, J=8.4 Hz, 2H), 6.80 (d, J=8.1 Hz, 1H), 4.55 (hept, J=6.2 Hz, 1H), 4.30-4.10 (m, 1H), 3.94-3.75 (m, 1H), 3.62-3.46 (m, 1H), 3.48-3.33 (m, 6H), 3.30-3.16 (m, 1H), 2.75 (d, J=10.8 Hz, 1H), 2.67-2.57 (m, 1H), 2.55 (d, J=11.1 Hz, 1H), 2.47-2.27 (m, 1H), 2.20 (s, 3H), 1.98 (d, J=7.3 Hz, 2H), 1.91-1.76 (m, 1H), 1.76-1.61 (m, 4H), 1.57-1.39 (m, 3H), 1.34 (d, J=6.0 Hz, 6H).

Workup

  1. stirringthe reaction mixture stirred for 16 h
  2. washwashed with 1N NaOH (100 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-02e609f11ce34b5bb115a2dc6f3b09e3
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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