Formaldehyde → HCID 57968591, compound

HRID 882762Notes

Reaction equation

HRID 882762 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C@@H:14]3[CH2:18][C@H:17]([O:19][C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH2:16][NH:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[CH2:27]=O.[Na]>C(O)C.[OH-].[Na+]>[CH3:27][N:15]1[CH2:16][C@@H:17]([O:19][C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[CH2:18][C@H:14]1[C:12]([N:8]1[CH2:9][CH2:10][CH2:11][N:5]([CH:1]2[CH2:2][CH2:3][CH2:4]2)[CH2:6][CH2:7]1)=[O:13]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5360545SodiumHCID 44601159HCID 44601159, compound

Product 1

HCID 57968591HCID 57968591, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of (2S,4S)-2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-(4-fluoro-phenoxy)-pyrrolidine (26 mg, 0.072 mmol) in ethanol (EtOH; 1 mL) was added formaldehyde (37% in H2O; 150 μL) and sodium triacetoxyborohyrdide (46 mg, 0.216 mmol). After 18 h, the mixture was diluted with 1 M NaOH and, stirred for 1 h, and extracted with CH2Cl2 (3×). The combined organic layers were dried and concentrated. Purification by FCC provided the desired product (17 mg, 63%). MS (ESI): mass calcd. for C21H30FN3O2, 375.23; m/z found, 376.6 [M+H]+. 1H NMR (CDCl3): 6.97-6.91 (m, 2H), 6.80-6.73 (m, 2H), 4.77-4.70 (m, 1H), 3.85-3.53 (m, 4H), 3.37 (dd, J=10.7, 3.8 Hz, 1H), 3.15 (ddd, J=8.9, 8.8, 2.7 Hz, 1H), 2.88-2.78 (m, 1H), 2.66-2.57 (m, 1H), 2.51-2.44 (m, 3H), 2.40 (dd, J=10.9, 5.2 Hz, 2H), 2.35 (s, 3H), 2.16-2.07 (m, 1H), 2.06-1.98 (m, 2H), 1.91-1.78 (m, 4H), 1.71-1.56 (m, 2H).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. customThe combined organic layers were dried
  3. concentrationconcentrated
  4. customPurification by FCC

Sources & evidence

ORD record
ord-b8c5c3464def4cb08f47f0c5f5aa49b5
Source dataset
uspto-grants-2012_08
Patent number
US08236792B2

Reaction notes

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