Sodium Hydroxide → HCID 178482601, compound

HRID 2306779Notes

Reaction equation

HRID 2306779 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][CH:11]([CH2:13][NH:14][C@H:15]3[CH2:20][CH2:19][C@H:18]([C:21]4[CH:30]=[CH:29][C:24]5[NH:25][C:26](=[O:28])[O:27][C:23]=5[CH:22]=4)[CH2:17][CH2:16]3)[O:10][N:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+].[BH-](OC(C)=O)(OC(C)=O)O[C:35](C)=O.[Na+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:12][CH:11]([CH2:13][N:14]([CH3:35])[C@H:15]3[CH2:16][CH2:17][C@H:18]([C:21]4[CH:30]=[CH:29][C:24]5[NH:25][C:26](=[O:28])[O:27][C:23]=5[CH:22]=4)[CH2:19][CH2:20]3)[O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 14798Sodium Hydroxide2×HCID 5049666Sodium triacetoxyborohydrideHCID 178518604HCID 178518604, compound

Product 1

HCID 178482601HCID 178482601, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of trans-6-(4-{[3-(4-fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-amino}-cyclohexyl)-3H-benzoxazol-2-one (51) (190 mg, 0.464 mmol) from Step 7, p-formaldehyde (70 mg, 2.32 mmol), and 2N NaOH (1 mL) in MeOH (15 mL) was stirred for 3 hours, NaBH(OAc)3 (138 mg, 0.650 mmol) was added, and the reaction mixture was stirred overnight. Solid NaOH was added until the solution turned clear. The reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (silica gel, 95:5:1 CH2Cl2:MeOH:NH4OH) gave trans-6-(4-{[3-(4-fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-methyl-amino}-cyclohexyl)-3H-benzoxazol-2-one (52) (60 mg, 31%), as a white foam: mp 109-114° C.; IR (KBr): 3430, 2927, 1772 cm−1; 1H NMR (500 MHz, DMSO-d6) δ 7.74 (dd, J=6, 3 Hz, 2H), 7.27 (m, 2H), 7.13 (s, 1H), 6.97 (m, 2H), 4.55 (m, 1H), 3.33 (m, 2H), 3.18 (m, 2H), 2.56 (m, 1H), 2.44 (m, 1H), 2.28 (s, 3H), 1.87 (m, 4H), 1.38 (m, 2H), 1.26 (m, 2H); API-MS (m/z): 424 [M+H]+; HRMS-API (m/z): [M+H]+ calcd for C24H26FN3O3, 424.2036; found, 424.2036; HPLC: method A, 5.39 minutes (98.1%); method B, 10.86 minutes (>99%).

Workup

  1. stirringthe reaction mixture was stirred overnight
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customPurification by flash chromatography (silica gel, 95:5:1 CH2Cl2:MeOH:NH4OH)

Sources & evidence

ORD record
ord-ccb65a3d595b488ba4270d7fb5a3eeae
Source dataset
uspto-grants-2004_12
Patent number
US06828341B2

Reaction notes

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